Defining cell type-specific immune responses in a mouse model of allergic contact dermatitis by single-cell transcriptomics
- State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, China
- Zhejiang Yangshengtang Institute of Natural Medication Co Ltd, China
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, China
- Yang Sheng Tang (Anji) Cosmetics Co Ltd, China
- Department of Dermatology, The First Affiliated Hospital of Fujian Medical University, China
- Department of Dermatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, China
Figures
Figure 1 with 1 supplement
Characterization of mouse allergic skin immune response by single cell RNA transcriptomic analysis.
(A) Overview of the experimental setting. Allergic contact dermatitis (ACD)-like skin inflammation was triggered by sequential sensitization and elicitation of ACD by topical application of 1% or …
Figure 1—figure supplement 1
Establishment of the DNFB-elicited ACD mouse model.
(A) Phenotypical presentation of mouse back skin after 0 hr, 12 hr, 24 hr, 36 hr and 60 hr of treatment. (B–C) Ear skin samples from control, ACD (24 hr) and ACD (60 hr) groups were subjected for …
Figure 2 with 1 supplement
T cells are primarily polarized to the IFNγ-producing type-1 inflammatory phenotype in ACD.
(A) tSNE plots showing cell distribution of the CD45+CD3+ or THY1+ T cell population after re-clustering. (B) Bar graphs showing the percentage of each T cell sub-cluster in the control and the ACD …
Figure 2—figure supplement 1
Characterization of T cell activation in ACD.
(A) Bubble plots showing the expression of marker genes for each cell cluster. Abbreviations: Treg, regulatory T cell; δγT, delta gamma T cell; ILC, innate lymphoid cell; NK, natural killer cell; NKT…
Figure 3 with 1 supplement
Characterization of myeloid cell activation in ACD.
(A) Stacked bar graphs showing the percentage of indicated myeloid cell populations in the control and the ACD samples. (B) Violin plots showing the expression of indicated genes across major skin …
Figure 3—figure supplement 1
Analysis of myeloid cell activation in ACD.
(A) Violin plots showing the expression of indicated genes across major skin resident and immune cells as indicated. (B) FACS plots showing the percentage of CD11B-FcεR1a+IL4/13+ (mast cell) or …
Figure 4 with 1 supplement
Characterization of the immune response of dermal fibroblasts in ACD.
(A) tSNE plots showing cell distribution of the Pdgfra+ dermal fibroblasts after re-clustering. (B) Bubble plots showing the expression of marker genes for each dFB cell cluster. Abbreviations: AP, …
Figure 4—figure supplement 1
Characterization of the immune response of dermal fibroblasts in ACD.
(A) Stacked bar graphs showing the percentage of each dFB sub-cluster in the control and the ACD samples. (B–C) Bubble plots (B) or Violin plots (C) showing the expression of indicated genes across …
Figure 5 with 1 supplement
Interaction between dFBs and T cells via the IFNG-CXCL10-CXCR3 signaling axis in ACD.
(A) Circle plot from cell-chat analysis showing the inferred intercellular communication network for IFNγ-IFNGR signaling in the control and the ACD cells. (B–C) Primary neonatal dFBs were treated …
Figure 5—figure supplement 1
Interaction between dFBs and T cells via the IFNG-CXCL10-CXCR3 signaling axis in ACD.
(A) Venn diagram comparing the top 100 lFNγ signaling dependent genes upregulated in the active vitiligo mouse dFBs (Xu et al., 2022), the top 100 genes enriched in the pAd (dFB_r5) cells, and the …
Figure 6 with 1 supplement
Targeted deletion of Ifngr in dFBs inhibited the development of type-1 skin inflammation in ACD.
(A) Tamoxifen-inducible targeted deletion of Ifngr1 in PDGFRA+ fibroblasts (Ifngr1FB-iKO) was achieved by crossing Ifngr1f/f and Pdgfra-cre/ERT mice, and mice were subjected to DNFB-induced ACD …
Figure 6—figure supplement 1
Targeted deletion of Ifngr1 in dFBs inhibited the development of type-1 skin inflammation in ACD.
(A–B) Lesional skin samples were immunostained with IFNGR1 and PDGFRA (A), and quantified result (B) showing the expression of IFNGR1 or PDGFRA in PDGFRA+ dFB or PDGFRA- dermal cells as indicated …
Figure 7 with 1 supplement
Activation of dermal T cells and fibroblasts in human ACD skin samples.
(A) Skin sections from healthy control (HC) or ACD human skin samples were immunostained with antibodies against CD4 (green), CD8 (blue), and IFNγ (red) (representative of n=4/group). Nuclei were …
Figure 7—figure supplement 1
Activation of dermal T cells and fibroblasts in human ACD skin samples.
(A) Skin sections from ACD human skin samples were immunostained with antibodies against CD4 (green), CD8 (blue) and IFNγ (red) (n=4). Nuclei were counter stained by DAPI (white). Scale bar, 200 μm. …
Additional files
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MDAR checklist
- https://cdn.elifesciences.org/articles/94698/elife-94698-mdarchecklist1-v2.pdf
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Supplementary file 1
List of gene primers used for RT-qPCR.
- https://cdn.elifesciences.org/articles/94698/elife-94698-supp1-v2.docx
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Supplementary file 2
List of Top 5 enriched genes in cell clusters shown in Figure 1B–C.
- https://cdn.elifesciences.org/articles/94698/elife-94698-supp2-v2.xlsx
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Supplementary file 3
List of the differentially upregulated genes in the active vitiligo mouse dFBs, the ACD pAd (dFB_r5) cells, and the IFNγ-stimulated primary dFBs as shown in Figure 5—figure supplement 1A.
- https://cdn.elifesciences.org/articles/94698/elife-94698-supp3-v2.xlsx
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Supplementary file 4
The RNA-seq FPKM data of primary neonatal dFBs treated with IFNγ, IL4 or IL17A.
- https://cdn.elifesciences.org/articles/94698/elife-94698-supp4-v2.xlsx
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Supplementary file 5
List of the differentially upregulated genes in primary neonatal dFBs treated with IFNγ, IL4 or IL17A as shown in Figure 5B–C.
- https://cdn.elifesciences.org/articles/94698/elife-94698-supp5-v2.xlsx
