Pivotal role of dermal γδ T Cells in the pathogenesis of psoriasis (101.24)

Abstract

Abstract Interleukin (IL)-23 and CD4+ Th17 cells are thought to be critical in the development of psoriasis. Here, we report that IL-23 predominantly stimulates innate dermal γδ T cells to produce IL-17 that leads to disease progression. Dermal γδ T cells constitutively express high levels of IL-23R, transcriptional factor RORγt, and various chemokine receptors. However, dermal γδ T cells are CD27 negative and do not produce IFN-γ. IL-17 production from dermal γδ T cells is independent of αβ T cells. The epidermal hyperplasia and inflammation induced by IL-23 is significantly decreased in TCR δKO and IL-17RA KO mice but occurs normally in TCR αKO mice. The clinical manifestations including epidermal thickening and neutrophil infiltration in an Imiquimod (IMQ)-induced mouse model of psoriasis are also significantly decreased in TCR δKO mice. Perhaps further promoting disease progression, IL-23 preferentially stimulates dermal γδ T cell expansion in vitro. In human psoriasis patients, γδ T cells are also greatly increased in affected skin and similarly produce large amounts of IL-17. Thus, IL-23-responsive dermal γδ T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.