Lymphocytes are a type of cell found in the blood that can detect and fight infections: in particular, some of them can leave the bloodstream to enter infected or inflamed tissues. To do so, these lymphocytes use proteins on their surface to roll along the inside wall of the blood vessel; then they stick to this wall and finally they pass through it. For some types of lymphocytes the details of this mechanism – such as precisely which surface proteins are necessary – remain unclear.

Here, Lee et al. collect human lymphocytes from the blood of healthy donors, and they identify a subgroup of lymphocytes, called MAIT cells, that are particularly good at moving from blood to infected or inflamed tissues, and further experiments reveal the types of surface proteins that help them do so.

Some of these proteins, for example selectin ligands, are important so the MAIT cell can roll on the wall of the blood vessel. Others, like CCR6, are essential for the cell to stop rolling and stick to the wall. Lee et al. also identify C/EBPδ, a regulatory protein inside the MAIT cell that controls how these other two types of proteins are produced. Finally, Lee et al. show that additional proteins, such as CCR2, are necessary for the lymphocyte to cross the vessel wall.

The proteins that help lymphocytes move from blood to tissues represent important targets to fight diseases. For example, blocking these proteins could prevent lymphocytes from invading and damaging healthy tissues, which happens in autoimmune diseases like multiple sclerosis. Alternatively, manipulating these proteins could help to engineer lymphocytes that can invade and kill tumor tissues in cancers.

The phenotypes and functions of peripheral T cells are intimately linked to the cells’ localization and patterns of migration (Masopust and Schenkel, 2013). For memory-phenotype T cells, these relationships were the basis of the dichotomous schema describing central (T_CM) and effector (T_EM) memory cells (Sallusto et al., 1999). The relationships among position, migration and function have also been emphasized in recent studies characterizing tissue resident memory T cells and recirculating memory T cells (Bromley et al., 2013; Fan and Rudensky, 2016; Gerlach et al., 2016; Masopust and Picker, 2012; Masopust and Schenkel, 2013). Elegant experiments in mice have shown that resident memory T cells can have critical roles in protection at barrier sites (Jiang et al., 2012). Less well defined have been the cells within the memory-phenotype population that can be recruited from the blood to an inflamed site in the very early stages of an immune response (Masopust and Picker, 2012). Nonetheless, these ‘first responders’ can play essential roles in tissue defense (Kohlmeier et al., 2008; Maloy et al., 2000; Wakim et al., 2008).

The recruitment of leukocytes to tissue from blood has been described within the longstanding paradigm, derived primarily from studies of neutrophils, of a multistep process of the cells’ rolling, followed by arrest, crawling, and diapedesis (Ley et al., 2007). An abundance of data support roles for selectins and their ligands in rolling, and for stimulated chemoattractant receptors and consequent integrin activation in firm arrest and extravasation (Springer, 1994). For trafficking of T_EM cells to sites of inflammation, P- and E-selectins on endothelial cells and their glycosylated counter-ligands on T cells mediate rolling, which initiates the process (Ley and Kansas, 2004; Sperandio et al., 2009). The best characterized ligands for P- and E-selectin are proteins, such as PSGL-1 (mouse and human), CD43 (mouse and human), ESL-1(mouse), and CD44 (mouse) that bear sugars containing sialyl Lewis^x (sLe^x), a tetrasaccharide consisting of N-acetylglucosamine, fucose, galactose, and sialic acid (Mondal et al., 2013; Phillips et al., 1990). The ability of leukocytes to display selectin ligands is determined primarily by the expression of glycosyltransferases responsible for synthesizing the appropriate glycoforms. These enzymes include core 2 β1,6-N-acetylglucosaminyltransferases, α1,3-fucosyltransferases, and α2,3-sialyltransferases (Ley and Kansas, 2004; Sperandio et al., 2009). Although the necessary enzymes and a full complement of selectin ligands are expressed constitutively on myeloid cells, expression on lymphocyte populations is heterogeneous and can be affected by cellular activation and differentiation (Austrup et al., 1997; Ley and Kansas, 2004; Wagers et al., 1998). Studies of mouse CD4⁺ T cells and/or cell lines have shown high preferential expression of selectin ligands on Th1 versus Th2 cells (Austrup et al., 1997; Blander et al., 1999), and counter-regulation of the α1,3-fucosyltransferase gene Fut7 by T-bet and GATA-3 (Chen et al., 2006); and Fut7 can be induced in mouse CD4⁺ T cells in response to a number of cytokines, including IL-12 and TGF-β1(Ebel et al., 2015; Ebel and Kansas, 2016). Little else is known about the molecular mechanisms regulating the expression of these glycosyltransferases in T cells.

Selectin-mediated rolling allows leukocytes to sample the endothelium for seven-transmembrane domain receptor agonists, principally chemokines, and for ligands, such as VCAM-1, MAdCAM-1, and ICAM-1, for the α4β1, α4β7, and β2 integrins, respectively (Springer, 1994). Although signals induced by selectin ligands on neutrophils can yield an integrin conformation sufficient to support integrin-mediated rolling (but not firm arrest), this is not observed for lymphocytes (Alon and Ley, 2008). Moreover, except for integrins on recently activated/effector T cells (Shulman et al., 2011), integrin activation that is sufficient to induce firm arrest under flow requires chemoattractant receptor-transduced signals (Alon and Ley, 2008). Chemokine receptors not only induce integrin activation and leukocyte arrest, but also directly mediate transendothelial migration (TEM) (Cinamon et al., 2001; Shulman et al., 2011). Among the 19 G-protein-coupled chemokine receptors, only two, CXCR4 and CCR7, are expressed on all naive T cells, whereas T cells with the effector/memory phenotype can express these and most of the remaining chemokine receptors, resulting in a high degree of combinatorial diversity (Bachelerie et al., 2014). The expanded repertoire of chemokine receptors on these cells confers the potential to traffic to and within the wide range of inflammatory sites generated during host defense and injury. There is, however, relatively little understanding of how multiple chemokine receptors can cooperate to provide the functions required by specific T cell subsets, and how the expression of selectin ligands, chemokine receptors and integrins are co-regulated on memory-phenotype T cells in order to confer the ability to extravasate efficiently.

Within the migratory T cell population, the initial cells to enter inflamed tissue should share a T_EM phenotype, including not only MHC class I/II restricted cells, but also innate-like T cell such as blood-borne subsets of γ/δ T cells (Hayday, 2000), and mucosal-associated invariant T (MAIT) cells (Gapin, 2014). In our previous studies, we characterized the subset of human CD4⁺ T cells co-expressing the chemokine receptors CCR5 and CCR2 (Zhang et al., 2010). These cells also express multiple inflammation-associated chemokine receptors and have features of a stable population of highly differentiated cells well equipped to serve as early responding T_EM. In extending these observations to CD8⁺ T cells, as described below, we found that most human CD8α⁺CCR2⁺ T cells were MAIT cells. MAIT cells are innate-like T cells that express Vα7.2-Jα33 (TRAV1-2-TRAJ33 according to the IMGT/GENE-DB nomenclature (Giudicelli et al., 2005) as part of a semi-invariant TCR (Franciszkiewicz et al., 2016; Porcelli et al., 1993), and recognize bacterial metabolites of riboflavin in the context of the non-polymorphic MR1 (Kjer-Nielsen et al., 2012). Under homeostatic conditions, MAIT cells are found in the intestinal lamina propria and liver, and represent a significant percentage of CD8⁺, memory-phenotype T cells in human blood. MAIT cells exhibit potent antibacterial activity and accumulate at sites of bacterial infections (Gold et al., 2010; Le Bourhis et al., 2010; Meierovics et al., 2013). MAIT cells may also have roles in immune-mediated diseases (Hinks, 2016). Although based on their expression of chemokine receptors and other surface markers, MAIT cells have been characterized as tissue-homing (Dusseaux et al., 2011), there are no detailed studies of their trafficking behavior.

Human MAIT cells have generally been identified by their co-expression of TCRVα7.2 and the NK cell marker CD161 (Franciszkiewicz et al., 2016). The discovery of the MR1-bound ligands for the MAIT cell TCRs has allowed for the development of MR1 tetramers (Reantragoon et al., 2013). Although these tetramers represent a significant new tool for studying MAIT cells, recent data show that the tetramers of MR1 bound to riboflavin- and folate-derived ligands can also identify a heterogeneous collection of Vα7.2^- non-MAIT cells, thereby defining a broader population including both MAIT cells and ‘atypical’ Vα7.2^- MR1-restricted T cells (Gherardin et al., 2016; Meermeier et al., 2016). The vast majority of MAIT cells in human blood are CD8α⁺ (many of which are also CD8β^low), and other than expression of CD8, no differences have been noted between CD8⁺ and CD8^- MAIT cells (Franciszkiewicz et al., 2016; Walker et al., 2012). For the sake of brevity, because the work described below deals only with the MAIT cells that are CD8α⁺, we will use ‘MAIT’ in place of ‘CD8α⁺ MAIT’.

In our current work, we found that MAIT cells were highly efficient at extravasation across inflamed endothelium. We also discovered that MAIT cells selectively and highly express the bZIP transcription factor C/EBPδ. siRNA-mediated knockdown of C/EBPδ showed that C/EBPδ contributed to the expression of glycosyltransferases/selectin ligands as well as CCR6 on MAIT cells, and consequently was required for optimal rolling and arrest of these cells on activated endothelial cells. Although these effects led to a decrease in the number of MAIT cells crossing the endothelium, knocking down C/EBPδ had no separate effect on the final and critical step of transendothelial migration - which depended on CCR2. Taken together, our data show that MAIT cells are efficient at trafficking across inflamed endothelium due to a coordinated program, regulated in part by C/EBPδ,that controls genes encoding proteins of disparate activities, each contributing to the migratory phenotype.

Our data demonstrate heterogeneous, graded expression of the components mediating extravasation into peripheral tissue within populations of human T cells. The abilities to roll, arrest and migrate across an inflamed endothelial cell layer are not all or none and reflect both qualitative and quantitative differences in expression of the essential components, with naïve and MAIT cells occupying extreme positions along a spectrum.

We found that the efficiency of the initial steps of rolling in the flow chamber assays were a function of the levels of surface selectin ligands and sLe^x, which in turn correlated with expression of FUT7 and ST3GAL4.

FucT-VII is the fucosyltransferase that is critical for synthesis of selectin ligands (Knibbs et al., 1996; Malý et al., 1996; Smithson et al., 2001). In particular, the level of FucT-VII is the determining factor in synthesis of E-selectin ligands (Knibbs et al., 1996; Ley and Kansas, 2004; Wagers et al., 1996). The mouse and/or human genes for FucT-VII are induced in proliferating T cells (Blander et al., 1999; Knibbs et al., 1996), up-regulated by IL-12 (Ebel et al., 2015; Wagers et al., 1998; White et al., 2001), and suppressed by IL-4 (Wagers et al., 1998), related to the activities of T-bet and GATA-3 (Chen et al., 2006). Among sialyltransferases, ST3Gal-IV (Ellies et al., 2002; Sperandio et al., 2006), together with ST3Gal-VI (Yang et al., 2012), are the critical enzymes for synthesizing selectin ligands in mice, whereas ST3Gal-IV is the dominant sialyltransferase in synthesizing selectin ligands on myeloid cells in humans (Mondal et al., 2015). Like the mouse Fut7 and/or human FUT7, St3gal4 is induced by T cell activation (Blander et al., 1999). However, little is known about how the mouse or human gene for ST3Gal-IV is regulated.

In concert with the progressive increase that we found among the memory-phenotype T cell subsets in levels of selectin ligands and rolling, we found enhanced abilities for firm arrest that could not be explained by differences in integrin expression. Antibody neutralization of the CCR6 ligand, CCL20, resulted in decreased numbers of cells arresting in flow chambers. Our findings are consistent with reports describing the ability of CCR6 to mediate arrest of lymphocytes, including, very recently, MAIT cells on adhesion-molecule coated plates and/or activated endothelial cells (Alcaide et al., 2012; Campbell et al., 1998; Fitzhugh et al., 2000; Ghannam et al., 2011; Kim et al., 2017). Of particular interest, the other chemokine receptors on the CD8α⁺ T cells could not substitute for CCR6 in maintaining optimal firm arrest, nor was CCR6/CCL20 necessary for TEM of those cells showing CCR6-independent arrest. On the CD8α⁺ T cells, therefore, CCR6 has a particular role in triggering firm arrest.

CCR6 is notable as the chemokine receptor that is expressed on all T cells that can make IL-17 (Acosta-Rodriguez et al., 2007; Singh et al., 2008), and CCR6 has been shown to be important for Th17 cell arrest on ICAM-1 (Alcaide et al., 2012). In addition to the Th17 cell regulator RORγt, only STAT5A (Tsuruyama et al., 2016) and, from our own work, PLZF (Singh et al., 2015) have been described as controlling CCR6. Based on our experiments using siRNA knockdown and ChIP, we have now identified C/EBPδ as an additional, direct activator of CCR6.

The pertussis-toxin resistant arrest that we observed in the memory-phenotype T cell subsets could be viewed as a ‘baseline’ activity on which inducible integrin activation can be superimposed. Although we are not aware of pertussis-toxin resistant arrest being reported previously for resting memory-phenotype cells, this phenomenon has been described for human effector T cells produced by activation ex vivo (Shulman et al., 2011). For those cells, unlike for the CCR6⁺ CD8α⁺ memory-phenotype T cells, there was no pertussis toxin sensitive component to the firm arrest, and their behavior was ascribed to high levels of integrin expression together with constitutive activity of PLC-γ1 (Shulman et al., 2011). Non-integrin mediated adhesion is another possibility (Schneider-Hohendorf et al., 2014). We have not investigated the mechanism responsible for the pertussis toxin resistant component of arrest by these resting cells, but our data suggest that in this regard the memory-phenotype CD8α⁺ T cells occupy a position intermediate between naïve and activated effector cells.

We found that blocking CCR5 did not affect the T cells’ arrest, nor did it prevent cells from undergoing TEM over the 20 min of observation. However, the data indicated that CCR5 functioned to shorten the time between the initiation of crawling and TEM, which, in vivo, would be presumed to speed extravasation. Consistent with our observations, CCR5 has been found not to contribute to leukocyte adhesion, either in flow chambers or in blood vessels (Diacovo et al., 2005; Shulman et al., 2011; Weber et al., 2001), but nonetheless to have roles in completing the process of extravasation (Diacovo et al., 2005).

For CCR2, our data showed a critical and specific role in TEM. We often observed significant TEM not only in the CCR2⁺ MAIT cells, but also in the CCR2^-/low MAIT cells. We presume that the CCR2^low MAIT cells within the CCR2^-/low MAIT cell samples accounted for the ability of cells in these samples to perform TEM. Because the number of CCR2^-/low MAIT cells that we obtained from an individual donor was often inadequate for the flow chamber studies, thereby limiting the number of studies that we could do with these cells, we have not used the CCR2 antagonist to test the possibility that CCR2 was mediating TEM in the CCR2^-/low cells.

Although CCR2 has been studied extensively in monocyte biology, relatively little is known about the role of CCR2 on T cells. It is of interest that on monocytes, CCR2 and CCL2 were also described as important for TEM (Weber et al., 1999), but not for firm adhesion (Huo et al., 2001; Weber et al., 1999). Of particular relevance for our studies, CCR2 was reported to be essential for TEM across HUVECs and human dermal microvascular endothelial cells in experiments using a mixed population of activated T cells (Shulman et al., 2011). We have previously shown that CCR2 is expressed on a subset of human CCR5⁺CD4⁺ T cells that have features of a stable population of highly differentiated long-term memory cells which, based on chemokine receptor expression, TCR activation threshold, and effector cytokine production, are ideally equipped for mediating rapid recall responses in tissue (Zhang et al., 2010). In addition, CD4⁺CCR5⁺CCR2⁺ T cells are found in cerebrospinal fluid associated with episodes of relapse in multiple sclerosis, and these cells demonstrate an enhanced ability to migrate across a model of the blood-brain barrier (Sato et al., 2012). Recent data in mice have suggested that CCR2 is important for the trafficking into the CNS of a pathological subset of Th17 cells that contributes to chronic and relapsing EAE (Kara et al., 2015). Taken together, the data suggest that - unlike for some other chemokine receptors that are associated with individual Th cell lineages - up-regulation of CCR2 (and CCR5) is part of a program directed specifically at conferring the capacity for migration of T cells into tissue.

Given the high degree of ligand/receptor promiscuity, the co-expression of many chemokines during inflammation, the co-expression of multiple chemokine receptors on individual cells, and the shared pathways for chemokine receptor signaling, studies of the chemokine system have often confronted questions of functional redundancy. Our data suggest that CCR6, CCR5, and CCR2 serve sequential and distinct functions in MAIT cell extravasation. From our experiments using anti-CCL20 antibodies, we can conclude that CCL20 is displayed on the surface of the TNFα-treated endothelial cells, and from the work of Shulman et al. (2011), we know that CCL2 is sequestered in endothelial cell vesicles and only available to CCR2 within T-cell-endothelial cell synapses. Taken together, these observations suggest that the separate roles for the receptors could be the result of anatomic segregation of their chemokine ligands, which might be a general feature of the chemokine system that limits functional redundancy.

Our interest in understanding the relationships between the expression of chemokine receptors such as CCR6 and CCR2 and the biology of T cell subsets led us to these studies of MAIT cells and their trafficking behavior. Our and/or others’ data (Dusseaux et al., 2011; Kim et al., 2017) showed that the MAIT cells were at the high end of a continuum among CD8α⁺ T cells as regards expression of selectin ligands and/or multiple tissue-homing chemokine receptors, and at the low end of a continuum as regards expression of CCR7 and CD62L, which are required for entering non-inflamed lymph nodes. The MAIT cells’ behavior on activated endothelial cells in the flow chamber assays and in vivo were fully consistent with an enhanced ability to enter inflamed tissue rapidly, without additional phenotypic changes and/or activation within lymphoid organs.

MAIT cells are able to make effector cytokines, and they contain cytotoxic molecules such as perforin, granulysin and granzymes (Dusseaux et al., 2011; Franciszkiewicz et al., 2016; Le Bourhis et al., 2013). MAIT cells are able to produce effector cytokines both in response to TCR activation and directly in response to cytokines such as IL-18 and IL-12 (Franciszkiewicz et al., 2016; Jo et al., 2014; Slichter et al., 2016; Ussher et al., 2014). These properties would allow MAIT cells to function locally within the earliest stages of antibacterial, and perhaps antiviral (Loh et al., 2016; van Wilgenburg et al., 2016) defense. In support of such a role, MAIT cells are decreased in blood of patients with bacterial pneumonias, and can be identified in M. tuberculosis-infected lungs (Le Bourhis et al., 2010).

We found that in MAIT cells, both FUT7 and ST3GAL4, as well as CCR6, are regulated in part by C/EBPδ, and our ChIP data suggest that FUT7, ST3GAL4, and CCR6 are direct targets of C/EBPδ. Knockdown of C/EBPδ resulted in decreased surface expression of both sLe^x and CCR6, although the resulting effects on numbers of rolling cells mediated by selectin ligands was more pronounced than on the specific step of firm arrest mediated in part by CCR6. Since the multiple steps of extravasation occur sequentially and interdependently, C/EBPδ’s regulation of rolling and firm arrest significantly affected numbers of cells migrating across the activated endothelial cells in the flow chamber assays. We presume that the effects that we documented in the flow chamber assays were the basis for the decreased entry of MAIT cells transfected with CEBPD siRNA into inflamed ears. We have summarized our findings for CCR2-expressing MAIT cells in the cartoon shown in Video 3.

Video 3

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Knockdown of C/EBPδ had no independent effect on the final step of MAIT cell TEM in the flow chamber assays, nor, consistent with this finding, on expression of CCR2 (or CCR5). Nonetheless, it is of interest that Yamamoto et al. described C/EBP binding sites 3’ to the CCR2 transcriptional start site that were important for CCR2 promoter activity and that could bind C/EBP proteins, including C/EBPδ, found in nuclear extracts of a human monocytic cell line (Yamamoto et al., 1999). These data suggest that our negative results notwithstanding, C/EBPδ might, in fact, have a role in regulating CCR2 expression in MAIT cells. Regardless, consideration of these data raises the important point that experiments using siRNA knockdown will typically underestimate roles of target genes given that mRNA and protein knockdown are incomplete both at the level of individual cells and across the heterogeneous population of siRNA-transfected cells. Consequently, our findings using siRNA knockdown of C/EBPδ reflect the lower limit of the activities of C/EBPδ in supporting expression of the glycosyltransferases and CCR6, and thereby MAIT cell trafficking.

We attributed the effect of knocking down C/EBPδ on the step of firm arrest to the decrease in expression of CCR6. Nonetheless, it is of interest that studies in mice have shown that ST3Gal-IV sialylates CXCR2 (Frommhold et al., 2008), and probably CCR1, and CCR5 (although not CCR2) (Döring et al., 2014). For these receptors, sialylation is important for chemokine-dependent activation. There is no evidence for sialylation of CCR6, but it remains possible that in addition to a decrease in expression of CCR6, knockdown of C/EBPδ could have led to diminished CCR6 function through loss of ST3Gal-IV-dependent sialylation. A role for glycosylation in CCR6 function warrants further study.

C/EBPδ is one of six members of the C/EBP family of bZIP transcription factors, each of which contains a basic DNA-binding domain and a ‘leucine zipper’ dimerization domain (Ramji and Foka, 2002). In mice, Cebpd is induced in many tissues in response to endotoxin or other inflammatory stimuli, including cytokines such as IL-6 and IL-1, although expression in these contexts is typically transient (Alam et al., 1992; Balamurugan and Sterneck, 2013; Ko et al., 2015). Studies in Cebpd knockout mice have demonstrated pleiotropic roles for C/EBPδ, including in multiple models of inflammation and infection (Yan et al., 2013; Chang et al., 2012; Duitman et al., 2012; Litvak et al., 2009). C/EBPδ has been implicated in the acute phase response (Alam et al., 1992; Juan et al., 1993; Ray and Ray, 1994) and in the phenotype and function of macrophages (Balamurugan et al., 2013; Chang et al., 2012; Duitman et al., 2012; Litvak et al., 2009; Maitra et al., 2011; Yan et al., 2013; Litvak et al., 2009; Maitra et al., 2011; Balamurugan et al., 2013). Of possible relevance to our own work, C/EBPδ has been suggested to enhance the migration of macrophages into infected lung (Duitman et al., 2012). A broader role for C/EBPδ in regulating leukocyte migration in inflammation is suggested by data on the C/EBPδ-mediated induction of chemokines, including the ligands for CCR6 (Chang et al., 2012) and CCR2 (Ko et al., 2014), and in the transcriptional response of endothelial cells to inflammatory stimuli (Hogan et al., 2017). In T cells, expression of CEBPD was detected in analyzing the transcriptome of human CD8⁺CD161⁺ T cells (Billerbeck et al., 2010), which would have included MAIT cells, and a bioinformatic analysis of the transcriptome and epigenetic modifications of human CD4⁺ T cells suggested that C/EBPδ might function as one of the ‘master regulators’ of T_EM differentiation (Durek et al., 2016). However, as far as we are aware, functional studies of C/EBPδ in T cells have not been previously reported.

Another transcription factor that has been described with an effect that is analogous but functionally inverse to C/EBPδ is Kruppel-like factor 2 (KLF2), which supports T cell trafficking to lymph nodes versus peripheral tissue by enhancing expression of CD62L and CCR7, and suppressing CXCR3 (Carlson et al., 2006; Preston et al., 2013). Similarly, SOCS1-mediated inhibition of STATs favors T cell trafficking to lymphoid organs versus peripheral tissue by enhancing expression of CCR7 and suppressing expression of CCR6 and CXCR3 (Yu et al., 2008). Based on our data, in contrast to these other factors, C/EBPδ is a positive regulator supporting the tissue-migrating phenotype.

Our study has some clear limitations that affect the generalizability of our conclusions. We studied only human MAIT cells from blood. Our ex vivo experiments used only a single type of endothelial cell (HUVEC) treated with a single pro-inflammatory activator (TNFα), and our in vivo experiments were limited to a simple and artificial model of inflammation at a single tissue site. It is possible that other endothelial cells and/or other activators would differentially affect the abilities of MAIT and non-MAIT cells to arrest and undergo TEM, and thereby reveal activities of other molecules, such as additional transcription factors and chemokine receptors, in these processes. Studies extended to more complex animal models would provide information on the performance of MAIT cells and the molecular mechanisms underlying their trafficking behavior in more biologically relevant models of inflammation. It will be of considerable interest to identify additional factors that control the program for extravasation and the interactions among overlapping networks specifying this activity in coordination with the fates and functions of effector-capable T cells. An understanding of the molecular species regulating the integration of migratory activity and other effector functions of such cells would suggest ways of enhancing or inhibiting T-cell mediated processes in peripheral tissues.

1. 1. Acosta-Rodriguez EV
   2. Rivino L
   3. Geginat J
   4. Jarrossay D
   5. Gattorno M
   6. Lanzavecchia A
   7. Sallusto F
   8. Napolitani G

   (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells

   Nature Immunology 8:639–646.

   https://doi.org/10.1038/ni1467

   • PubMed
   • Google Scholar
2. 1. Alam T
   2. An MR
   3. Papaconstantinou J

   (1992)

   Differential expression of three C/EBP isoforms in multiple tissues during the acute phase response

   The Journal of Biological Chemistry 267:5021–5024.

   • PubMed
   • Google Scholar
3. 1. Alcaide P
   2. Maganto-Garcia E
   3. Newton G
   4. Travers R
   5. Croce KJ
   6. Bu DX
   7. Luscinskas FW
   8. Lichtman AH

   (2012) Difference in Th1 and Th17 lymphocyte adhesion to endothelium

   The Journal of Immunology 188:1421–1430.

   https://doi.org/10.4049/jimmunol.1101647

   • PubMed
   • Google Scholar
4. 1. Alon R
   2. Ley K

   (2008) Cells on the run: shear-regulated integrin activation in leukocyte rolling and arrest on endothelial cells

   Current Opinion in Cell Biology 20:525–532.

   https://doi.org/10.1016/j.ceb.2008.04.003

   • PubMed
   • Google Scholar
5. 1. Austrup F
   2. Vestweber D
   3. Borges E
   4. Löhning M
   5. Bräuer R
   6. Herz U
   7. Renz H
   8. Hallmann R
   9. Scheffold A
   10. Radbruch A
   11. Hamann A

   (1997) P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflammed tissues

   Nature 385:81–83.

   https://doi.org/10.1038/385081a0

   • PubMed
   • Google Scholar
6. 1. Bachelerie F
   2. Ben-Baruch A
   3. Burkhardt AM
   4. Combadiere C
   5. Farber JM
   6. Graham GJ
   7. Horuk R
   8. Sparre-Ulrich AH
   9. Locati M
   10. Luster AD
   11. Mantovani A
   12. Matsushima K
   13. Murphy PM
   14. Nibbs R
   15. Nomiyama H
   16. Power CA
   17. Proudfoot AE
   18. Rosenkilde MM
   19. Rot A
   20. Sozzani S
   21. Thelen M
   22. Yoshie O
   23. Zlotnik A

   (2014) International union of basic and clinical pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors

   Pharmacological Reviews 66:1–79.

   https://doi.org/10.1124/pr.113.007724

   • PubMed
   • Google Scholar
7. 1. Balamurugan K
   2. Sharan S
   3. Klarmann KD
   4. Zhang Y
   5. Coppola V
   6. Summers GH
   7. Roger T
   8. Morrison DK
   9. Keller JR
   10. Sterneck E

   (2013) FBXW7α attenuates inflammatory signalling by downregulating C/EBPδ and its target gene Tlr4

   Nature Communications 4:1662.

   https://doi.org/10.1038/ncomms2677

   • PubMed
   • Google Scholar
8. 1. Balamurugan K
   2. Sterneck E

   (2013) The many faces of C/EBPδ and their relevance for inflammation and cancer

   International Journal of Biological Sciences 9:917–933.

   https://doi.org/10.7150/ijbs.7224

   • PubMed
   • Google Scholar
9. 1. Billerbeck E
   2. Kang YH
   3. Walker L
   4. Lockstone H
   5. Grafmueller S
   6. Fleming V
   7. Flint J
   8. Willberg CB
   9. Bengsch B
   10. Seigel B
   11. Ramamurthy N
   12. Zitzmann N
   13. Barnes EJ
   14. Thevanayagam J
   15. Bhagwanani A
   16. Leslie A
   17. Oo YH
   18. Kollnberger S
   19. Bowness P
   20. Drognitz O
   21. Adams DH
   22. Blum HE
   23. Thimme R
   24. Klenerman P

   (2010) Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties

   PNAS 107:3006–3011.

   https://doi.org/10.1073/pnas.0914839107

   • PubMed
   • Google Scholar
10. 1. Blander JM
    2. Visintin I
    3. Janeway CA
    4. Medzhitov R

    (1999)

    Alpha(1,3)-fucosyltransferase VII and alpha(2,3)-sialyltransferase IV are up-regulated in activated CD4 T cells and maintained after their differentiation into Th1 and migration into inflammatory sites

    Journal of Immunology 163:3746–3752.

    • Google Scholar
11. 1. Bromley SK
    2. Yan S
    3. Tomura M
    4. Kanagawa O
    5. Luster AD

    (2013) Recirculating memory T cells are a unique subset of CD4+ T cells with a distinct phenotype and migratory pattern

    The Journal of Immunology 190:970–976.

    https://doi.org/10.4049/jimmunol.1202805

    • PubMed
    • Google Scholar
12. 1. Campbell JJ
    2. Hedrick J
    3. Zlotnik A
    4. Siani MA
    5. Thompson DA
    6. Butcher EC

    (1998) Chemokines and the arrest of lymphocytes rolling under flow conditions

    Science 279:381–384.

    https://doi.org/10.1126/science.279.5349.381

    • PubMed
    • Google Scholar
13. 1. Carlson CM
    2. Endrizzi BT
    3. Wu J
    4. Ding X
    5. Weinreich MA
    6. Walsh ER
    7. Wani MA
    8. Lingrel JB
    9. Hogquist KA
    10. Jameson SC

    (2006) Kruppel-like factor 2 regulates thymocyte and T-cell migration

    Nature 442:299–302.

    https://doi.org/10.1038/nature04882

    • PubMed
    • Google Scholar
14. 1. Chang LH
    2. Huang HS
    3. Wu PT
    4. Jou IM
    5. Pan MH
    6. Chang WC
    7. Wang DD
    8. Wang JM

    (2012) Role of macrophage CCAAT/enhancer binding protein delta in the pathogenesis of rheumatoid arthritis in collagen-induced arthritic mice

    PLoS One 7:e45378.

    https://doi.org/10.1371/journal.pone.0045378

    • PubMed
    • Google Scholar
15. 1. Chen GY
    2. Osada H
    3. Santamaria-Babi LF
    4. Kannagi R

    (2006) Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes

    PNAS 103:16894–16899.

    https://doi.org/10.1073/pnas.0607926103

    • PubMed
    • Google Scholar
16. 1. Cinamon G
    2. Shinder V
    3. Alon R

    (2001) Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines

    Nature Immunology 2:515–522.

    https://doi.org/10.1038/88710

    • PubMed
    • Google Scholar
17. 1. Cosmi L
    2. De Palma R
    3. Santarlasci V
    4. Maggi L
    5. Capone M
    6. Frosali F
    7. Rodolico G
    8. Querci V
    9. Abbate G
    10. Angeli R
    11. Berrino L
    12. Fambrini M
    13. Caproni M
    14. Tonelli F
    15. Lazzeri E
    16. Parronchi P
    17. Liotta F
    18. Maggi E
    19. Romagnani S
    20. Annunziato F

    (2008) Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor

    The Journal of Experimental Medicine 205:1903–1916.

    https://doi.org/10.1084/jem.20080397

    • PubMed
    • Google Scholar
18. 1. Diacovo TG
    2. Blasius AL
    3. Mak TW
    4. Cella M
    5. Colonna M

    (2005) Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes

    The Journal of Experimental Medicine 202:687–696.

    https://doi.org/10.1084/jem.20051035

    • PubMed
    • Google Scholar
19. 1. Döring Y
    2. Noels H
    3. Mandl M
    4. Kramp B
    5. Neideck C
    6. Lievens D
    7. Drechsler M
    8. Megens RT
    9. Tilstam PV
    10. Langer M
    11. Hartwig H
    12. Theelen W
    13. Marth JD
    14. Sperandio M
    15. Soehnlein O
    16. Weber C

    (2014) Deficiency of the sialyltransferase St3Gal4 reduces Ccl5-mediated myeloid cell recruitment and arrest: short communication

    Circulation Research 114:976–981.

    https://doi.org/10.1161/CIRCRESAHA.114.302426

    • PubMed
    • Google Scholar
20. 1. Duitman J
    2. Hoogendijk AJ
    3. Groot AP
    4. Ruela de Sousa RR
    5. van der Poll T
    6. Florquin S
    7. Spek CA

    (2012) CCAAT-enhancer binding protein delta (C/EBPδ) protects against Klebsiella pneumoniae-induced pulmonary infection: potential role for macrophage migration

    The Journal of Infectious Diseases 206:1826–1835.

    https://doi.org/10.1093/infdis/jis615

    • PubMed
    • Google Scholar
21. 1. Durek P
    2. Nordström K
    3. Gasparoni G
    4. Salhab A
    5. Kressler C
    6. de Almeida M
    7. Bassler K
    8. Ulas T
    9. Schmidt F
    10. Xiong J
    11. Glažar P
    12. Klironomos F
    13. Sinha A
    14. Kinkley S
    15. Yang X
    16. Arrigoni L
    17. Amirabad AD
    18. Ardakani FB
    19. Feuerbach L
    20. Gorka O
    21. Ebert P
    22. Müller F
    23. Li N
    24. Frischbutter S
    25. Schlickeiser S
    26. Cendon C
    27. Fröhler S
    28. Felder B
    29. Gasparoni N
    30. Imbusch CD
    31. Hutter B
    32. Zipprich G
    33. Tauchmann Y
    34. Reinke S
    35. Wassilew G
    36. Hoffmann U
    37. Richter AS
    38. Sieverling L
    39. Chang HD
    40. Syrbe U
    41. Kalus U
    42. Eils J
    43. Brors B
    44. Manke T
    45. Ruland J
    46. Lengauer T
    47. Rajewsky N
    48. Chen W
    49. Dong J
    50. Sawitzki B
    51. Chung HR
    52. Rosenstiel P
    53. Schulz MH
    54. Schultze JL
    55. Radbruch A
    56. Walter J
    57. Hamann A
    58. Polansky JK
    59. DEEP Consortium

    (2016) Epigenomic profiling of human CD4⁺T cells supports a linear differentiation model and highlights molecular regulators of memory development

    Immunity 45:1148–1161.

    https://doi.org/10.1016/j.immuni.2016.10.022

    • PubMed
    • Google Scholar
22. 1. Dusseaux M
    2. Martin E
    3. Serriari N
    4. Péguillet I
    5. Premel V
    6. Louis D
    7. Milder M
    8. Le Bourhis L
    9. Soudais C
    10. Treiner E
    11. Lantz O

    (2011) Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells

    Blood 117:1250–1259.

    https://doi.org/10.1182/blood-2010-08-303339

    • PubMed
    • Google Scholar
23. 1. Ebel ME
    2. Awe O
    3. Kaplan MH
    4. Kansas GS

    (2015) Diverse inflammatory cytokines induce selectin ligand expression on murine CD4 T cells via p38α MAPK

    The Journal of Immunology 194:5781–5788.

    https://doi.org/10.4049/jimmunol.1500485

    • PubMed
    • Google Scholar
24. 1. Ebel ME
    2. Kansas GS

    (2016) Functions of smad transcription factors in TGF-β1-induced selectin ligand expression on murine CD4 Th cells

    The Journal of Immunology 197:2627–2634.

    https://doi.org/10.4049/jimmunol.1600723

    • PubMed
    • Google Scholar
25. 1. Ellies LG
    2. Sperandio M
    3. Underhill GH
    4. Yousif J
    5. Smith M
    6. Priatel JJ
    7. Kansas GS
    8. Ley K
    9. Marth JD

    (2002) Sialyltransferase specificity in selectin ligand formation

    Blood 100:3618–3625.

    https://doi.org/10.1182/blood-2002-04-1007

    • PubMed
    • Google Scholar
26. 1. Fan X
    2. Rudensky AY

    (2016) Hallmarks of tissue-resident lymphocytes

    Cell 164:1198–1211.

    https://doi.org/10.1016/j.cell.2016.02.048

    • PubMed
    • Google Scholar
27. 1. Fitzhugh DJ
    2. Naik S
    3. Caughman SW
    4. Hwang ST

    (2000) Cutting edge: C-C chemokine receptor 6 is essential for arrest of a subset of memory T cells on activated dermal microvascular endothelial cells under physiologic flow conditions in vitro

    The Journal of Immunology 165:6677–6681.

    https://doi.org/10.4049/jimmunol.165.12.6677

    • PubMed
    • Google Scholar
28. 1. Franciszkiewicz K
    2. Salou M
    3. Legoux F
    4. Zhou Q
    5. Cui Y
    6. Bessoles S
    7. Lantz O

    (2016) MHC class I-related molecule, MR1, and mucosal-associated invariant T cells

    Immunological Reviews 272:120–138.

    https://doi.org/10.1111/imr.12423

    • PubMed
    • Google Scholar
29. 1. Frommhold D
    2. Ludwig A
    3. Bixel MG
    4. Zarbock A
    5. Babushkina I
    6. Weissinger M
    7. Cauwenberghs S
    8. Ellies LG
    9. Marth JD
    10. Beck-Sickinger AG
    11. Sixt M
    12. Lange-Sperandio B
    13. Zernecke A
    14. Brandt E
    15. Weber C
    16. Vestweber D
    17. Ley K
    18. Sperandio M

    (2008) Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation

    The Journal of Experimental Medicine 205:1435–1446.

    https://doi.org/10.1084/jem.20070846

    • PubMed
    • Google Scholar
30. 1. Gapin L

    (2014) Check MAIT

    The Journal of Immunology 192:4475–4480.

    https://doi.org/10.4049/jimmunol.1400119

    • PubMed
    • Google Scholar
31. 1. Gerlach C
    2. Moseman EA
    3. Loughhead SM
    4. Alvarez D
    5. Zwijnenburg AJ
    6. Waanders L
    7. Garg R
    8. de la Torre JC
    9. von Andrian UH

    (2016) The chemokine receptor CX3CR1 defines three antigen-experienced cd8 t cell subsets with distinct roles in immune surveillance and homeostasis

    Immunity 45:1270–1284.

    https://doi.org/10.1016/j.immuni.2016.10.018

    • PubMed
    • Google Scholar
32. 1. Ghannam S
    2. Dejou C
    3. Pedretti N
    4. Giot JP
    5. Dorgham K
    6. Boukhaddaoui H
    7. Deleuze V
    8. Bernard FX
    9. Jorgensen C
    10. Yssel H
    11. Pène J

    (2011) CCL20 and β-defensin-2 induce arrest of human Th17 cells on inflamed endothelium in vitro under flow conditions

    The Journal of Immunology 186:1411–1420.

    https://doi.org/10.4049/jimmunol.1000597

    • PubMed
    • Google Scholar
33. 1. Gherardin NA
    2. Keller AN
    3. Woolley RE
    4. Le Nours J
    5. Ritchie DS
    6. Neeson PJ
    7. Birkinshaw RW
    8. Eckle SBG
    9. Waddington JN
    10. Liu L
    11. Fairlie DP
    12. Uldrich AP
    13. Pellicci DG
    14. McCluskey J
    15. Godfrey DI
    16. Rossjohn J

    (2016) Diversity of T cells restricted by the MHC Class I-Related Molecule MR1 facilitates differential antigen recognition

    Immunity 44:32–45.

    https://doi.org/10.1016/j.immuni.2015.12.005

    • PubMed
    • Google Scholar
34. 1. Giudicelli V
    2. Chaume D
    3. Lefranc MP

    (2005) IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes

    Nucleic Acids Research 33:D256–D261.

    https://doi.org/10.1093/nar/gki010

    • PubMed
    • Google Scholar
35. 1. Gold MC
    2. Cerri S
    3. Smyk-Pearson S
    4. Cansler ME
    5. Vogt TM
    6. Delepine J
    7. Winata E
    8. Swarbrick GM
    9. Chua WJ
    10. Yu YY
    11. Lantz O
    12. Cook MS
    13. Null MD
    14. Jacoby DB
    15. Harriff MJ
    16. Lewinsohn DA
    17. Hansen TH
    18. Lewinsohn DM

    (2010) Human mucosal associated invariant T cells detect bacterially infected cells

    PLoS Biology 8:e1000407.

    https://doi.org/10.1371/journal.pbio.1000407

    • PubMed
    • Google Scholar
36. 1. Hayday AC

    (2000) [gamma][delta] cells: a right time and a right place for a conserved third way of protection

    Annual Review of Immunology 18:975–1026.

    https://doi.org/10.1146/annurev.immunol.18.1.975

    • PubMed
    • Google Scholar
37. 1. Hidalgo A
    2. Peired AJ
    3. Wild M
    4. Vestweber D
    5. Frenette PS

    (2007) Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44

    Immunity 26:477–489.

    https://doi.org/10.1016/j.immuni.2007.03.011

    • PubMed
    • Google Scholar
38. 1. Hinks TS

    (2016) Mucosal-associated invariant T cells in autoimmunity, immune-mediated diseases and airways disease

    Immunology 148:1–12.

    https://doi.org/10.1111/imm.12582

    • PubMed
    • Google Scholar
39. 1. Hogan NT
    2. Whalen MB
    3. Stolze LK
    4. Hadeli NK
    5. Lam MT
    6. Springstead JR
    7. Glass CK
    8. Romanoski CE

    (2017) Transcriptional networks specifying homeostatic and inflammatory programs of gene expression in human aortic endothelial cells

    eLife 6:e22536.

    https://doi.org/10.7554/eLife.22536

    • PubMed
    • Google Scholar
40. 1. Huo Y
    2. Weber C
    3. Forlow SB
    4. Sperandio M
    5. Thatte J
    6. Mack M
    7. Jung S
    8. Littman DR
    9. Ley K

    (2001) The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium

    Journal of Clinical Investigation 108:1307–1314.

    https://doi.org/10.1172/JCI12877

    • PubMed
    • Google Scholar
41. 1. Jiang X
    2. Clark RA
    3. Liu L
    4. Wagers AJ
    5. Fuhlbrigge RC
    6. Kupper TS

    (2012) Skin infection generates non-migratory memory CD8+ T(RM) cells providing global skin immunity

    Nature 483:227–231.

    https://doi.org/10.1038/nature10851

    • PubMed
    • Google Scholar
42. 1. Jo J
    2. Tan AT
    3. Ussher JE
    4. Sandalova E
    5. Tang XZ
    6. Tan-Garcia A
    7. To N
    8. Hong M
    9. Chia A
    10. Gill US
    11. Kennedy PT
    12. Tan KC
    13. Lee KH
    14. De Libero G
    15. Gehring AJ
    16. Willberg CB
    17. Klenerman P
    18. Bertoletti A

    (2014) Toll-like receptor 8 agonist and bacteria trigger potent activation of innate immune cells in human liver

    PLoS Pathogens 10:e1004210.

    https://doi.org/10.1371/journal.ppat.1004210

    • PubMed
    • Google Scholar
43. 1. Juan TS
    2. Wilson DR
    3. Wilde MD
    4. Darlington GJ

    (1993) Participation of the transcription factor C/EBP delta in the acute-phase regulation of the human gene for complement component C3

    PNAS 90:2584–2588.

    https://doi.org/10.1073/pnas.90.7.2584

    • PubMed
    • Google Scholar
44. 1. Kara EE
    2. McKenzie DR
    3. Bastow CR
    4. Gregor CE
    5. Fenix KA
    6. Ogunniyi AD
    7. Paton JC
    8. Mack M
    9. Pombal DR
    10. Seillet C
    11. Dubois B
    12. Liston A
    13. MacDonald KP
    14. Belz GT
    15. Smyth MJ
    16. Hill GR
    17. Comerford I
    18. McColl SR

    (2015) CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells

    Nature Communications 6:8644.

    https://doi.org/10.1038/ncomms9644

    • PubMed
    • Google Scholar
45. 1. Kim M
    2. Yoo SJ
    3. Kang SW
    4. Kwon J
    5. Choi I
    6. Lee CH

    (2017) TNFα and IL-1β in the synovial fluid facilitate mucosal-associated invariant T (MAIT) cell migration

    Cytokine 99:91–98.

    https://doi.org/10.1016/j.cyto.2017.07.007

    • PubMed
    • Google Scholar
46. 1. Kjer-Nielsen L
    2. Patel O
    3. Corbett AJ
    4. Le Nours J
    5. Meehan B
    6. Liu L
    7. Bhati M
    8. Chen Z
    9. Kostenko L
    10. Reantragoon R
    11. Williamson NA
    12. Purcell AW
    13. Dudek NL
    14. McConville MJ
    15. O'Hair RA
    16. Khairallah GN
    17. Godfrey DI
    18. Fairlie DP
    19. Rossjohn J
    20. McCluskey J

    (2012) MR1 presents microbial vitamin B metabolites to MAIT cells

    Nature 491:717–723.

    https://doi.org/10.1038/nature11605

    • PubMed
    • Google Scholar
47. 1. Knibbs RN
    2. Craig RA
    3. Natsuka S
    4. Chang A
    5. Cameron M
    6. Lowe JB
    7. Stoolman LM

    (1996) The fucosyltransferase FucT-VII regulates E-selectin ligand synthesis in human T cells

    The Journal of Cell Biology 133:911–920.

    https://doi.org/10.1083/jcb.133.4.911

    • PubMed
    • Google Scholar
48. 1. Ko CY
    2. Chang WC
    3. Wang JM

    (2015) Biological roles of CCAAT/Enhancer-binding protein delta during inflammation

    Journal of Biomedical Science 22:6.

    https://doi.org/10.1186/s12929-014-0110-2

    • PubMed
    • Google Scholar
49. 1. Ko CY
    2. Wang WL
    3. Wang SM
    4. Chu YY
    5. Chang WC
    6. Wang JM

    (2014) Glycogen synthase kinase-3β-mediated CCAAT/enhancer-binding protein delta phosphorylation in astrocytes promotes migration and activation of microglia/macrophages

    Neurobiology of Aging 35:24–34.

    https://doi.org/10.1016/j.neurobiolaging.2013.07.021

    • PubMed
    • Google Scholar
50. 1. Kohlmeier JE
    2. Miller SC
    3. Smith J
    4. Lu B
    5. Gerard C
    6. Cookenham T
    7. Roberts AD
    8. Woodland DL

    (2008) The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell response to respiratory virus infections

    Immunity 29:101–113.

    https://doi.org/10.1016/j.immuni.2008.05.011

    • PubMed
    • Google Scholar
51. 1. Le Bourhis L
    2. Dusseaux M
    3. Bohineust A
    4. Bessoles S
    5. Martin E
    6. Premel V
    7. Coré M
    8. Sleurs D
    9. Serriari NE
    10. Treiner E
    11. Hivroz C
    12. Sansonetti P
    13. Gougeon ML
    14. Soudais C
    15. Lantz O

    (2013) MAIT cells detect and efficiently lyse bacterially-infected epithelial cells

    PLoS Pathogens 9:e1003681.

    https://doi.org/10.1371/journal.ppat.1003681

    • PubMed
    • Google Scholar
52. 1. Le Bourhis L
    2. Martin E
    3. Péguillet I
    4. Guihot A
    5. Froux N
    6. Coré M
    7. Lévy E
    8. Dusseaux M
    9. Meyssonnier V
    10. Premel V
    11. Ngo C
    12. Riteau B
    13. Duban L
    14. Robert D
    15. Huang S
    16. Rottman M
    17. Soudais C
    18. Lantz O

    (2010) Antimicrobial activity of mucosal-associated invariant T cells

    Nature Immunology 11:701–708.

    https://doi.org/10.1038/ni.1890

    • PubMed
    • Google Scholar
53. 1. Ley K
    2. Kansas GS

    (2004) Selectins in T-cell recruitment to non-lymphoid tissues and sites of inflammation

    Nature Reviews Immunology 4:325–336.

    https://doi.org/10.1038/nri1351

    • PubMed
    • Google Scholar
54. 1. Ley K
    2. Laudanna C
    3. Cybulsky MI
    4. Nourshargh S

    (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated

    Nature Reviews Immunology 7:678–689.

    https://doi.org/10.1038/nri2156

    • PubMed
    • Google Scholar
55. 1. Litvak V
    2. Ramsey SA
    3. Rust AG
    4. Zak DE
    5. Kennedy KA
    6. Lampano AE
    7. Nykter M
    8. Shmulevich I
    9. Aderem A

    (2009) Function of C/EBPdelta in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals

    Nature Immunology 10:437–443.

    https://doi.org/10.1038/ni.1721

    • PubMed
    • Google Scholar
56. 1. Loh L
    2. Wang Z
    3. Sant S
    4. Koutsakos M
    5. Jegaskanda S
    6. Corbett AJ
    7. Liu L
    8. Fairlie DP
    9. Crowe J
    10. Rossjohn J
    11. Xu J
    12. Doherty PC
    13. McCluskey J
    14. Kedzierska K

    (2016) Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation

    PNAS 113:10133–10138.

    https://doi.org/10.1073/pnas.1610750113

    • PubMed
    • Google Scholar
57. 1. Maitra U
    2. Gan L
    3. Chang S
    4. Li L

    (2011) Low-dose endotoxin induces inflammation by selectively removing nuclear receptors and activating CCAAT/enhancer-binding protein δ

    The Journal of Immunology 186:4467–4473.

    https://doi.org/10.4049/jimmunol.1003300

    • PubMed
    • Google Scholar
58. 1. Malý P
    2. Thall A
    3. Petryniak B
    4. Rogers CE
    5. Smith PL
    6. Marks RM
    7. Kelly RJ
    8. Gersten KM
    9. Cheng G
    10. Saunders TL
    11. Camper SA
    12. Camphausen RT
    13. Sullivan FX
    14. Isogai Y
    15. Hindsgaul O
    16. von Andrian UH
    17. Lowe JB

    (1996) The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis

    Cell 86:643–653.

    https://doi.org/10.1016/S0092-8674(00)80137-3

    • PubMed
    • Google Scholar
59. 1. Maloy KJ
    2. Burkhart C
    3. Junt TM
    4. Odermatt B
    5. Oxenius A
    6. Piali L
    7. Zinkernagel RM
    8. Hengartner H

    (2000) CD4(+) T cell subsets during virus infection. Protective capacity depends on effector cytokine secretion and on migratory capability

    The Journal of Experimental Medicine 191:2159–2170.

    https://doi.org/10.1084/jem.191.12.2159

    • PubMed
    • Google Scholar
60. 1. Martin E
    2. Treiner E
    3. Duban L
    4. Guerri L
    5. Laude H
    6. Toly C
    7. Premel V
    8. Devys A
    9. Moura IC
    10. Tilloy F
    11. Cherif S
    12. Vera G
    13. Latour S
    14. Soudais C
    15. Lantz O

    (2009) Stepwise development of MAIT cells in mouse and human

    PLoS Biology 7:e1000054.

    https://doi.org/10.1371/journal.pbio.1000054

    • PubMed
    • Google Scholar
61. 1. Masopust D
    2. Picker LJ

    (2012) Hidden memories: frontline memory T cells and early pathogen interception

    The Journal of Immunology 188:5811–5817.

    https://doi.org/10.4049/jimmunol.1102695

    • PubMed
    • Google Scholar
62. 1. Masopust D
    2. Schenkel JM

    (2013) The integration of T cell migration, differentiation and function

    Nature Reviews Immunology 13:309–320.

    https://doi.org/10.1038/nri3442

    • PubMed
    • Google Scholar
63. 1. Meermeier EW
    2. Laugel BF
    3. Sewell AK
    4. Corbett AJ
    5. Rossjohn J
    6. McCluskey J
    7. Harriff MJ
    8. Franks T
    9. Gold MC
    10. Lewinsohn DM

    (2016) Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens

    Nature Communications 7:12506.

    https://doi.org/10.1038/ncomms12506

    • PubMed
    • Google Scholar
64. 1. Meierovics A
    2. Yankelevich WJ
    3. Cowley SC

    (2013) MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection

    PNAS 110:E3119–E3128.

    https://doi.org/10.1073/pnas.1302799110

    • PubMed
    • Google Scholar
65. 1. Mondal N
    2. Buffone A
    3. Neelamegham S

    (2013) Distinct glycosyltransferases synthesize E-selectin ligands in human vs. mouse leukocytes

    Cell Adhesion & Migration 7:288–292.

    https://doi.org/10.4161/cam.24714

    • PubMed
    • Google Scholar
66. 1. Mondal N
    2. Buffone A
    3. Stolfa G
    4. Antonopoulos A
    5. Lau JT
    6. Haslam SM
    7. Dell A
    8. Neelamegham S

    (2015) ST3Gal-4 is the primary sialyltransferase regulating the synthesis of E-, P-, and L-selectin ligands on human myeloid leukocytes

    Blood 125:687–696.

    https://doi.org/10.1182/blood-2014-07-588590

    • PubMed
    • Google Scholar
67. 1. Phillips ML
    2. Nudelman E
    3. Gaeta FC
    4. Perez M
    5. Singhal AK
    6. Hakomori S
    7. Paulson JC

    (1990) ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex

    Science 250:1130–1132.

    https://doi.org/10.1126/science.1701274

    • PubMed
    • Google Scholar
68. 1. Porcelli S
    2. Yockey CE
    3. Brenner MB
    4. Balk SP

    (1993) Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8- alpha/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain

    Journal of Experimental Medicine 178:1–16.

    https://doi.org/10.1084/jem.178.1.1

    • PubMed
    • Google Scholar
69. 1. Preston GC
    2. Feijoo-Carnero C
    3. Schurch N
    4. Cowling VH
    5. Cantrell DA

    (2013) The impact of KLF2 modulation on the transcriptional program and function of CD8 T cells

    PLoS One 8:e77537.

    https://doi.org/10.1371/journal.pone.0077537

    • PubMed
    • Google Scholar
70. 1. Ramji DP
    2. Foka P

    (2002) CCAAT/enhancer-binding proteins: structure, function and regulation

    Biochemical Journal 365:561–575.

    https://doi.org/10.1042/bj20020508

    • PubMed
    • Google Scholar
71. 1. Ray A
    2. Ray BK

    (1994) Serum amyloid A gene expression under acute-phase conditions involves participation of inducible C/EBP-beta and C/EBP-delta and their activation by phosphorylation

    Molecular and Cellular Biology 14:4324–4332.

    https://doi.org/10.1128/MCB.14.6.4324

    • PubMed
    • Google Scholar
72. 1. Reantragoon R
    2. Corbett AJ
    3. Sakala IG
    4. Gherardin NA
    5. Furness JB
    6. Chen Z
    7. Eckle SB
    8. Uldrich AP
    9. Birkinshaw RW
    10. Patel O
    11. Kostenko L
    12. Meehan B
    13. Kedzierska K
    14. Liu L
    15. Fairlie DP
    16. Hansen TH
    17. Godfrey DI
    18. Rossjohn J
    19. McCluskey J
    20. Kjer-Nielsen L

    (2013) Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells

    The Journal of Experimental Medicine 210:2305–2320.

    https://doi.org/10.1084/jem.20130958

    • PubMed
    • Google Scholar
73. 1. Sallusto F
    2. Lenig D
    3. Förster R
    4. Lipp M
    5. Lanzavecchia A

    (1999) Two subsets of memory T lymphocytes with distinct homing potentials and effector functions

    Nature 401:708–712.

    https://doi.org/10.1038/44385

    • PubMed
    • Google Scholar
74. 1. Sato W
    2. Tomita A
    3. Ichikawa D
    4. Lin Y
    5. Kishida H
    6. Miyake S
    7. Ogawa M
    8. Okamoto T
    9. Murata M
    10. Kuroiwa Y
    11. Aranami T
    12. Yamamura T

    (2012) CCR2(+)CCR5(+) T cells produce matrix metalloproteinase-9 and osteopontin in the pathogenesis of multiple sclerosis

    The Journal of Immunology 189:5057–5065.

    https://doi.org/10.4049/jimmunol.1202026

    • PubMed
    • Google Scholar
75. 1. Schneider-Hohendorf T
    2. Rossaint J
    3. Mohan H
    4. Böning D
    5. Breuer J
    6. Kuhlmann T
    7. Gross CC
    8. Flanagan K
    9. Sorokin L
    10. Vestweber D
    11. Zarbock A
    12. Schwab N
    13. Wiendl H

    (2014) VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells

    The Journal of Experimental Medicine 211:1833–1846.

    https://doi.org/10.1084/jem.20140540

    • PubMed
    • Google Scholar
76. 1. Shulman Z
    2. Cohen SJ
    3. Roediger B
    4. Kalchenko V
    5. Jain R
    6. Grabovsky V
    7. Klein E
    8. Shinder V
    9. Stoler-Barak L
    10. Feigelson SW
    11. Meshel T
    12. Nurmi SM
    13. Goldstein I
    14. Hartley O
    15. Gahmberg CG
    16. Etzioni A
    17. Weninger W
    18. Ben-Baruch A
    19. Alon R

    (2011) Transendothelial migration of lymphocytes mediated by intraendothelial vesicle stores rather than by extracellular chemokine depots

    Nature Immunology 13:67–76.

    https://doi.org/10.1038/ni.2173

    • PubMed
    • Google Scholar
77. 1. Singh SP
    2. Zhang HH
    3. Foley JF
    4. Hedrick MN
    5. Farber JM

    (2008) Human T cells that are able to produce IL-17 express the chemokine receptor CCR6

    The Journal of Immunology 180:214–221.

    https://doi.org/10.4049/jimmunol.180.1.214

    • Google Scholar
78. 1. Singh SP
    2. Zhang HH
    3. Tsang H
    4. Gardina PJ
    5. Myers TG
    6. Nagarajan V
    7. Lee CH
    8. Farber JM

    (2015) PLZF regulates CCR6 and is critical for the acquisition and maintenance of the Th17 phenotype in human cells

    The Journal of Immunology 194:4350–4361.

    https://doi.org/10.4049/jimmunol.1401093

    • PubMed
    • Google Scholar
79. 1. Slichter CK
    2. McDavid A
    3. Miller HW
    4. Finak G
    5. Seymour BJ
    6. McNevin JP
    7. Diaz G
    8. Czartoski JL
    9. McElrath MJ
    10. Gottardo R
    11. Prlic M

    (2016) Distinct activation thresholds of human conventional and innate-like memory T cells

    JCI Insight 1:.

    https://doi.org/10.1172/jci.insight.86292

    • PubMed
    • Google Scholar
80. 1. Smithson G
    2. Rogers CE
    3. Smith PL
    4. Scheidegger EP
    5. Petryniak B
    6. Myers JT
    7. Kim DS
    8. Homeister JW
    9. Lowe JB

    (2001) Fuc-TVII is required for T helper 1 and T cytotoxic 1 lymphocyte selectin ligand expression and recruitment in inflammation, and together with Fuc-TIV regulates naive T cell trafficking to lymph nodes

    The Journal of Experimental Medicine 194:601–614.

    https://doi.org/10.1084/jem.194.5.601

    • PubMed
    • Google Scholar
81. 1. Sperandio M
    2. Frommhold D
    3. Babushkina I
    4. Ellies LG
    5. Olson TS
    6. Smith ML
    7. Fritzsching B
    8. Pauly E
    9. Smith DF
    10. Nobiling R
    11. Linderkamp O
    12. Marth JD
    13. Ley K

    (2006) Alpha 2,3-sialyltransferase-IV is essential for L-selectin ligand function in inflammation

    European Journal of Immunology 36:3207–3215.

    https://doi.org/10.1002/eji.200636157

    • PubMed
    • Google Scholar
82. 1. Sperandio M
    2. Gleissner CA
    3. Ley K

    (2009) Glycosylation in immune cell trafficking

    Immunological Reviews 230:97–113.

    https://doi.org/10.1111/j.1600-065X.2009.00795.x

    • PubMed
    • Google Scholar
83. 1. Springer TA

    (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm

    Cell 76:301–314.

    https://doi.org/10.1016/0092-8674(94)90337-9

    • PubMed
    • Google Scholar
84. 1. Tsuruyama T
    2. Hiratsuka T
    3. Aini W
    4. Nakamura T

    (2016) STAT5A modulates chemokine receptor CCR6 expression and enhances Pre-B Cell Growth in a CCL20-Dependent Manner

    Journal of Cellular Biochemistry 117:2630–2642.

    https://doi.org/10.1002/jcb.25558

    • PubMed
    • Google Scholar
85. 1. Ussher JE
    2. Bilton M
    3. Attwod E
    4. Shadwell J
    5. Richardson R
    6. de Lara C
    7. Mettke E
    8. Kurioka A
    9. Hansen TH
    10. Klenerman P
    11. Willberg CB

    (2014) CD161++ CD8+ T cells, including the MAIT cell subset, are specifically activated by IL-12+IL-18 in a TCR-independent manner

    European Journal of Immunology 44:195–203.

    https://doi.org/10.1002/eji.201343509

    • PubMed
    • Google Scholar
86. 1. van Wilgenburg B
    2. Scherwitzl I
    3. Hutchinson EC
    4. Leng T
    5. Kurioka A
    6. Kulicke C
    7. de Lara C
    8. Cole S
    9. Vasanawathana S
    10. Limpitikul W
    11. Malasit P
    12. Young D
    13. Denney L
    14. Moore MD
    15. Fabris P
    16. Giordani MT
    17. Oo YH
    18. Laidlaw SM
    19. Dustin LB
    20. Ho LP
    21. Thompson FM
    22. Ramamurthy N
    23. Mongkolsapaya J
    24. Willberg CB
    25. Screaton GR
    26. Klenerman P
    27. STOP-HCV consortium

    (2016) MAIT cells are activated during human viral infections

    Nature Communications 7:11653.

    https://doi.org/10.1038/ncomms11653

    • PubMed
    • Google Scholar
87. 1. Wagers AJ
    2. Lowe JB
    3. Kansas GS

    (1996)

    An important role for the alpha 1,3 fucosyltransferase, FucT-VII, in leukocyte adhesion to E-selectin

    Blood 88:2125–2132.

    • PubMed
    • Google Scholar
88. 1. Wagers AJ
    2. Waters CM
    3. Stoolman LM
    4. Kansas GS

    (1998) Interleukin 12 and interleukin 4 control T cell adhesion to endothelial selectins through opposite effects on alpha1, 3-fucosyltransferase VII gene expression

    The Journal of Experimental Medicine 188:2225–2231.

    https://doi.org/10.1084/jem.188.12.2225

    • PubMed
    • Google Scholar
89. 1. Wakim LM
    2. Gebhardt T
    3. Heath WR
    4. Carbone FR

    (2008) Cutting edge: local recall responses by memory T cells newly recruited to peripheral nonlymphoid tissues

    The Journal of Immunology 181:5837–5841.

    https://doi.org/10.4049/jimmunol.181.9.5837

    • PubMed
    • Google Scholar
90. 1. Walker LJ
    2. Kang YH
    3. Smith MO
    4. Tharmalingham H
    5. Ramamurthy N
    6. Fleming VM
    7. Sahgal N
    8. Leslie A
    9. Oo Y
    10. Geremia A
    11. Scriba TJ
    12. Hanekom WA
    13. Lauer GM
    14. Lantz O
    15. Adams DH
    16. Powrie F
    17. Barnes E
    18. Klenerman P

    (2012) Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells

    Blood 119:422–433.

    https://doi.org/10.1182/blood-2011-05-353789

    • PubMed
    • Google Scholar
91. 1. Weber C
    2. Weber KS
    3. Klier C
    4. Gu S
    5. Wank R
    6. Horuk R
    7. Nelson PJ

    (2001) Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and T(H)1-like/CD45RO(+) T cells

    Blood 97:1144–1146.

    https://doi.org/10.1182/blood.V97.4.1144

    • PubMed
    • Google Scholar
92. 1. Weber KS
    2. von Hundelshausen P
    3. Clark-Lewis I
    4. Weber PC
    5. Weber C

    (1999) Differential immobilization and hierarchical involvement of chemokines in monocyte arrest and transmigration on inflamed endothelium in shear flow

    European Journal of Immunology 29:700–712.

    https://doi.org/10.1002/(SICI)1521-4141(199902)29:02<700::AID-IMMU700>3.0.CO;2-1

    • PubMed
    • Google Scholar
93. 1. White SJ
    2. Underhill GH
    3. Kaplan MH
    4. Kansas GS

    (2001) Cutting edge: differential requirements for Stat4 in expression of glycosyltransferases responsible for selectin ligand formation in Th1 cells

    The Journal of Immunology 167:628–631.

    https://doi.org/10.4049/jimmunol.167.2.628

    • PubMed
    • Google Scholar
94. 1. Yamamoto K
    2. Takeshima H
    3. Hamada K
    4. Nakao M
    5. Kino T
    6. Nishi T
    7. Kochi M
    8. Kuratsu J
    9. Yoshimura T
    10. Ushio Y

    (1999) Cloning and functional characterization of the 5'-flanking region of the human monocyte chemoattractant protein-1 receptor (CCR2) gene. Essential role of 5'-untranslated region in tissue-specific expression

    The Journal of Biological Chemistry 274:4646–4654.

    https://doi.org/10.1074/jbc.274.8.4646

    • PubMed
    • Google Scholar
95. 1. Yan C
    2. Johnson PF
    3. Tang H
    4. Ye Y
    5. Wu M
    6. Gao H

    (2013) CCAAT/enhancer-binding protein δ is a critical mediator of lipopolysaccharide-induced acute lung injury

    The American Journal of Pathology 182:420–430.

    https://doi.org/10.1016/j.ajpath.2012.10.013

    • PubMed
    • Google Scholar
96. 1. Yang WH
    2. Nussbaum C
    3. Grewal PK
    4. Marth JD
    5. Sperandio M

    (2012) Coordinated roles of ST3Gal-VI and ST3Gal-IV sialyltransferases in the synthesis of selectin ligands

    Blood 120:1015–1026.

    https://doi.org/10.1182/blood-2012-04-424366

    • PubMed
    • Google Scholar
97. 1. Yao L
    2. Pan J
    3. Setiadi H
    4. Patel KD
    5. McEver RP

    (1996) Interleukin 4 or oncostatin M induces a prolonged increase in P-selectin mRNA and protein in human endothelial cells

    Journal of Experimental Medicine 184:81–92.

    https://doi.org/10.1084/jem.184.1.81

    • PubMed
    • Google Scholar
98. 1. Yu CR
    2. Mahdi RM
    3. Liu X
    4. Zhang A
    5. Naka T
    6. Kishimoto T
    7. Egwuagu CE

    (2008) SOCS1 regulates CCR7 expression and migration of CD4+ T cells into peripheral tissues

    The Journal of Immunology 181:1190–1198.

    https://doi.org/10.4049/jimmunol.181.2.1190

    • PubMed
    • Google Scholar
99. 1. Zhang HH
    2. Song K
    3. Rabin RL
    4. Hill BJ
    5. Perfetto SP
    6. Roederer M
    7. Douek DC
    8. Siegel RM
    9. Farber JM

    (2010) CCR2 identifies a stable population of human effector memory CD4+ T cells equipped for rapid recall response

    The Journal of Immunology 185:6646–6663.

    https://doi.org/10.4049/jimmunol.0904156

    • PubMed
    • Google Scholar

Author details

1. Chang Hoon Lee

   Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

   Present address

   Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon, Korea

   Contribution

   Formal analysis, Investigation, Visualization, Writing—original draft

   Contributed equally with

   Hongwei H Zhang

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-8953-9069

2. Hongwei H Zhang

   Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

   Contribution

   Formal analysis, Validation, Investigation, Visualization

   Contributed equally with

   Chang Hoon Lee

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-7298-8802

3. Satya P Singh

   Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

   Contribution

   Validation, Investigation

   Competing interests

   No competing interests declared

4. Lily Koo

   Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

   Present address

   Center for Devices and Radiological Health, U.S. Food and Drug Administration, Maryland, United States

   Contribution

   Investigation, Visualization

   Competing interests

   No competing interests declared

5. Juraj Kabat

   Biological Imaging Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

   Contribution

   Software, Visualization

   Competing interests

   No competing interests declared

6. Hsinyi Tsang

   Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

   Present address

   Cancer Informatics Branch, National Cancer Institute, Rockville, United States

   Contribution

   Software, Visualization

   Competing interests

   No competing interests declared

7. Tej Pratap Singh

   Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

   Contribution

   Investigation

   Competing interests

   No competing interests declared

8. Joshua M Farber

   Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States

   Contribution

   Conceptualization, Supervision, Funding acquisition, Project administration, Writing—review and editing

   For correspondence

   jfarber@niaid.nih.gov

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-3224-0378

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