γδ T cell localization and abundance in canine atopic dermatitis: An RNA in situ hybridization study

Canine atopic dermatitis (cAD) is a common inflammatory skin disease with emerging evidence suggesting complex involvement of cytokine patterns including Th17-associated pathways. Gamma delta (γδ) T cells are innate-like lymphocytes capable of rapid interleukin (IL)-17 production, but their role in cAD remains less investigated. This prospective study aimed to localize IL-17F and IL-23 receptor (IL-23R) expression in relation to γδ T cells in the skin of dogs with cAD and to evaluate a SCART1-like RNA probe as a marker for γδ T cells. Skin biopsies were obtained from healthy control dogs (n = 4) and dogs with cAD (n = 5), including non-lesional and lesional sites. RNAscope along with protein co-detection was performed, and signals were quantified using confocal microscopy. cAD dogs had significantly increased dermal γδ T cells, compared to controls (P = 0.0055), with marked dermal enrichment of γδ T cells co-expressing IL-17F (P < 0.001). Epidermal differences between control and cAD were not significant. Similarly, IL-23R co-expression did not differ by disease status; however, epidermal γδ T cell IL-23R expression was inversely associated in lesional skin with owner reported pruritus severity. γδ T cells co-expressing SCART1-like RNA were increased in cAD and strongly correlated with total γδ T cell signal. In conclusion, our findings identify a potential dermal IL-17-associated γδ T cell axis in cAD and provide support for SCART1-like as a marker for canine γδ T cells in future work. Dermal γδ T cells may contribute to chronic inflammation and pruritus in cAD.