Homeostatic activation of aryl hydrocarbon receptor by dietary ligands dampens cutaneous allergic responses by controlling Langerhans cells migration

  1. Adeline Cros
  2. Alba De Juan
  3. Renaud Leclère
  4. Julio L Sampaio
  5. Mabel San Roman
  6. Mathieu Maurin
  7. Sandrine Heurtebise-Chrétien
  8. Elodie Segura  Is a corresponding author
  1. Institut Curie, PSL Research University, INSERM, U932, France
  2. Institut Curie, PSL Research University, Plateforme de Pathologie Expérimentale, France
  3. Institut Curie, PSL Research University, Plateforme de Métabolomique et Lipidomique, France
6 figures, 1 table and 1 additional file

Figures

Figure 1 with 1 supplement
Lack of dietary aryl hydrocarbon receptor (AhR) ligands exacerbates cutaneous allergic type 2 responses.

Mice were placed on AhR-poor diet or enriched in indole-3-carbinol (I3C diet) for 3 wk of adaptation prior to the start of experiments. (A–D) Papain or vehicle (PBS) was injected in the footpad at …

Figure 1—figure supplement 1
Comparable cutaneous allergic Th2 responses in mice fed with normal chow and indole-3-carbinol (I3C) diet.

Mice were placed on aryl hydrocarbon receptor (AhR)-poor or I3C diet for 3 wk of adaptation prior to the start of experiments. (A) Relative abundance of I3C was measured in the serum at day 0. …

Figure 2 with 1 supplement
Lack of dietary aryl hydrocarbon receptor (AhR) ligands does not impact airway allergic type 2 inflammation.

Mice were placed on AhR-poor or indole-3-carbinol (I3C) diet for 3 wk of adaptation prior to the start of experiments. Mice were exposed to papain or vehicle (PBS) intranasally four times at days 0, …

Figure 2—figure supplement 1
Gating strategy for bronchoalveolar cells.

Bronchoalveolar cells were gated on live singlets. One representative example for mice treated with vehicle (A) or papain (B).

Lack of dietary aryl hydrocarbon receptor (AhR) ligands worsens airway allergy after skin sensitization.

Mice were placed on AhR-poor or indole-3-carbinol (I3C) diet for 3 wk of adaptation prior to the start of experiments. Papain or vehicle (PBS) was injected in the footpad at day 0. At day 7, all …

Figure 4 with 1 supplement
Lack of dietary aryl hydrocarbon receptor (AhR) ligands impairs Langerhans cells migration, thereby increasing Th2 responses.

(A, B) Mice were placed on AhR-poor or indole-3-carbinol (I3C) diet for 3 wk of adaptation prior to the start of experiments. (A) Density of epidermal Langerhans cells was assessed by imaging Cd207(L…

Figure 4—figure supplement 1
Analysis of cutaneous allergy.

Mice were fed on aryl hydrocarbon receptor (AhR)-poor or indole-3-carbinol (I3C) diet for 3 wk of adaptation prior to the start of experiments. (A) Gating strategy for epidermal Langerhans cells. …

Figure 5 with 3 supplements
Dietary aryl hydrocarbon receptor (AhR) ligands regulate the inflammatory profile of epidermal cells.

Mice were placed on AhR-poor or indole-3-carbinol (I3C) diet for 3 wk of adaptation prior to the start of experiments. Papain or vehicle (PBS) was injected in the footpad at day 0. (A–D) After 6 hr, …

Figure 5—source data 1

List of differentially expressed genes between conditions.

https://cdn.elifesciences.org/articles/86413/elife-86413-fig5-data1-v2.xlsx
Figure 5—figure supplement 1
Dietary aryl hydrocarbon receptor (AhR) ligands modulate the transcriptomic profile of epidermal cells.

Mice were fed on AhR-poor or indole-3-carbinol (I3C) diet for 3 wk of adaptation prior to the start of experiments. Papain or vehicle (PBS) was injected in the footpad at day 0. After 6 hr, …

Figure 5—figure supplement 2
Diet-derived aryl hydrocarbon receptor (AhR) ligands do not impact keratinocyte barrier genes.

(A, B) RNA-seq data of the epidermis of germ-free or specific pathogen-free (SPF) mice (n = 8) was extracted from public source (GSE162925). Gene set enrichment analysis was performed for Gene …

Figure 5—figure supplement 3
Diet-derived aryl hydrocarbon receptor (AhR) ligands do not impact the structure of the skin barrier.

Mice were placed on AhR-poor diet or enriched in indole-3-carbinol (I3C diet) for 3 wk of adaptation prior to the start of experiments. (A) Papain or vehicle (PBS) was injected in the footpad at day …

Aryl hydrocarbon receptor (AhR) activation regulates keratinocyte production of TGF-β in mouse and human.

(A, B) Mice were placed on AhR-poor or indole-3-carbinol (I3C) diet for 3 wk of adaptation prior to the start of experiments. Papain or vehicle (PBS) was injected in the footpad at day 0. (A) After …

Tables

Key resources table
Reagent type (species) or resourceDesignationSource or referenceIdentifiersAdditional information
Strain, strain background (mouse)Cd207(Langerin)-eGFP-DTRKissenpfennig et al., 2005RRID:IMSR_JAX:016940Founder animals were donated by M.Vocanson (CIRI, Lyon, France)
Cell line (human) HaCaTWilson, 2014RRID:CVCL_0038
AntibodyAnti-TCRβ BUV737 (hamster monoclonal, clone H57-597)BD BiosciencesAB_27408181:200
AntibodyAnti-CD11c PerCpCy5.5 (hamster monoclonal, clone HL3)BD BiosciencesAB_17274221:200
AntibodyAnti-SiglecF BV480 (rat monoclonal, clone E50-2440)BD BiosciencesAB_27439401:200
AntibodyAnti-CD45 FITC (rat monoclonal, clone 30-F11)BioLegendAB_3129731:200
AntibodyAnti-CD11b Pe-CF594 (rat monoclonal, clone M1/70)BD BiosciencesAB_111544221:400
AntibodyAnti-MHCII BV786 (rat monoclonal, clone M5/114.15.2)BioLegendAB_25659771:200
AntibodyAnti-Ly6G BV605 (rat monoclonal, clone 1A8)BioLegendAB_25658801:200
AntibodyAnti-CD4 BV650 (rat monoclonal, clone RM4-5)BioLegendAB_25625291:200
AntibodyAnti-Ly6C AF700 (rat monoclonal, clone HK1.4)BioLegendAB_106432701:300
AntibodyAnti-EpCAM APCFire750 (rat monoclonal, clone G8.8)BioLegendAB_26297581:400
AntibodyAnti-CD11b PerCPCy5.5 (rat monoclonal, clone M1/70)BD BiosciencesAB_3940021:400
AntibodyAnti-TCRβ APC (hamster monoclonal, clone H57-597)BioLegendAB_3134351:200
AntibodyAnti-CD4 FITC (rat monoclonal, clone RM4-5)BD BiosciencesAB_3945821:200
AntibodyAnti-CD19 APC-Cy7 (rat monoclonal, clone 1D3)BD BiosciencesAB_3967701:200
AntibodyAnti-CD172a BUV737 (rat monoclonal, clone P84)BD BiosciencesAB_28711541:200
AntibodyAnti-CD19 BV480 (rat monoclonal, clone 1D3)BD BiosciencesAB_27395091:200
AntibodyAnti-CD3 BV480 (hamster monoclonal, clone 500A2)BD BiosciencesAB_27440351:200
AntibodyAnti-XCR1 BV510 (rat monoclonal, clone ZET)BioLegendAB_25652311:100
AntibodyAnti-CD11c BV785 (hamster monoclonal, clone N418)BioLegendAB_25652681:100
AntibodyAnti-CD86 FITC (rat monoclonal, clone GL1)BD BiosciencesAB_3949931:100
AntibodyAnti-CD26 PE (rat monoclonal, clone H194-112)BioLegendAB_22930471:200
AntibodyAnti-CD40 PerCP-efluor710 (rat monoclonal, clone 1C10)eBioscienceAB_25736771:100
AntibodyAnti-PDL2 APC (rat monoclonal, clone TY25)BioLegendAB_25663451:100
AntibodyAnti-MHC II BV650 (rat monoclonal, clone M5/114.15.2)BioLegendAB_25659751:400
Software, algorithmDESeq2Love et al., 2014v1.22.2
Software, algorithm GSEASubramanian et al., 2005v4.0.3
Software, algorithmQuPathBankhead et al., 2017v.0.3.1
Software, algorithm FlowJoFlowJo LLCv10

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