Fig. 2. RORγt⁺ γδT cells drive re-epithelialization through epidermal IL-17RC.

(A) Hematoxylin and eosin–stained tissue image (top) and ST plot of microarray spots (bottom) of unwounded and D3 wounded skin (unwounded, n = 1; wounded, n = 2). Scale bars, 200 μm. (B) UMAP plot and cluster annotation of ST spots based on marker genes in fig. S5. (C) γδ T/MAIT clusters are enriched in wound edge epithelium. P-value score table from MIA of D3 wounded ST clusters and CITE-seq effector lymphocyte clusters. Integrin α5⁺, K14⁺ migrating epidermal tongue length in unsplinted D3 wounds from Tcrd^CreER;Rorc^fl/fl and Rorc^fl/fl (D) (n ≥ 7, N = 3). Mr1^−/− and Mr1^Het (E) (n ≥ 4, N = 3). Cd4^Cre/−; Rorc^fl/fl and Cd4^Cre/− (F) (n = 5, N = 3). (G) γδ T/MAIT cell clusters dominantly express Il17a and Il17f. Dot plot of genes from D3 wounded skin CITE-seq analysis. Frequency of cells expressing stated gene (percent) and average expression per cluster (average). (H) rmIL-17A administration augments the re-epithelialization in GFP-KI mice. Experimental schematic (left) and quantification of D3 migrating tongue length of GFP-KI skin intradermally injected with rmIL-17A or PBS (right) (n = 4, N = 2). (I) Spatial plots of Il17rc and Il17ra reveal an up-regulation of these receptors at the wound’s edge. (J) IL-17RC expression on epithelial cells drives re-epithelialization. Quantification of migrating tongue length from splinted D3 wounds Krt14^Cre; Il17rc^fl/fl mice (n ≥ 5, N = 2). Significance was determined using a two-tailed t test and a 95% confidence interval.