Fig. 3: Mouse versus human epidermal lymphocytes subpopulation concerning epidermal CD8⁺ Tc17 and γδT17.

a UMAP visualization of 8545 lymphoid cells in mouse control epidermal skin (Mouse-CE, n = 3) and Ube2l3^△Epi epidermal skin (Mouse-UE, n = 3). Cell clusters: CD8T (CD8⁺ T cells), DETC (dendritic epidermal T cells), NK (natural killer cells), ILC (innate lymphoid cells), Unknown (unknown cells), Treg (regulatory T cells), gdT17 (IL-17A⁺ γδT cells), Cyc-T (cycling T cells), CD4 (CD4⁺ T cell). b Comparative percentages of cell clusters in CE vs. UE. n = 3 per group. c Dot plot of cluster-defining marker genes. d Integrated UMAPs of 35502 lymphoid cells of human cells. Subpopulations: CCL20_Tc17 (CCL20-expressing cytotoxic CD8⁺ T cells), CXCL13_Th17 (CXCL13-expressing Th17 cells), FOXP3_Treg (FOXP3⁺ regulatory T cells), GNLY_Tc (GNLY-expressing cytotoxic CD8⁺ T cells). e Composition of 15 human T-cell subsets (grouped into 8 categories) in normal epidermis (NE) vs. psoriatic epidermis (PE) by scRNA-seq. f Dot plot of representative genes expressed in T-cell subsets. KEGG enrichment of DEGs in (g) mouse gdT17 (UE vs. CE) and (h) human Tc17 (PE vs. NE) subsets. Red arrows indicate conserved pathways: T-cell receptor signaling, Th17 differentiation, Th1/Th2 differentiation. i PySCENIC transcription factor regulon activity in mouse γδT17. Rorc: one of top upregulated TF. j Top 10 concordant pathway signatures (GSVA) between PE_Tc17 and UE_gdT cluster after cross-species gene ortholog mapping. Correlation: R = 0.65, p = 0.049. k Top 10 discordant pathway signatures between PE_Tc17 and UE_gdT clusters. Correlation: R = 0.99, p < 2.2e⁻¹⁶. l Flow cytometry of TNFα and IL-17A in Epi-Ctrl and Epi-Ube2l3^△Epi. Bar graphs show proportions of: IL-17A⁺CD45⁺/CD45⁺ cells, IL-17A⁺CD3⁺/CD3⁺ T cells, IL-17A⁺αβT/αβT cells, IL-17A⁺γδT/γδT cells. n = 5/group. m, n Flow cytometry of TNFα and IL-17A in the epidermal lymphoid cells of healthy donors (Epi-HD) and psoriatic patients (Epi-PSO). Bar charts: IL-17A⁺ CD3⁺ /CD3⁺ T cells, TNFα⁺ CD3⁺ /CD3⁺ T, IL-17A⁺CD4⁺/IL-17A⁺CD3⁺ T cells, IL-17A⁺CD8⁺/ CD3⁺ T cells (HD, n = 5, PSO, n = 12). o Schematic of anti-IL-17A mAb or IgG on tamoxifen induced Ube2l3^△Epi mice (IgG: isotype control). p Phenotype and H&E staining (Week 4). Bar: epidermal thickness (IgG, n = 3, IL-17A mAb, n = 3). q Immunofluorence staining of CD3 and Loricrin in two group (scar bar:100 μm). Data are presented as mean ± SEM, and p-values were calculated by unpaired, two-tail student’s t-test (l, m, p), and paired, two-tail student’s t-test (m). Figure o was created in BioRender. Chen, X. (2025) https://BioRender.com/nc6wucr.