Abstract
Interleukin-23 (IL-23) and CD4(+) T helper 17 (Th17) cells are thought to be critical in psoriasis pathogenesis. Here, we report that IL-23 predominantly stimulated dermal γδ Tcells to produce IL-17 that led to disease progression. Dermal γδ Tcells constitutively expressed the IL-23 receptor (IL-23R) and transcriptional factor RORγt. IL-17 production from dermal γδ Tcells was independent of αβ Tcells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in Tcell receptor δ-deficient (Tcrd(-/-)) and IL-17 receptor-deficient (Il17ra(-/-)) mice but occurred normally in Tcra(-/-) mice. Imiquimod-induced skin pathology was also significantly decreased in Tcrd(-/-) mice. Perhaps further promoting disease progression, IL-23 stimulated dermal γδ Tcell expansion. In psoriasis patients, γδ Tcells were greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal γδ Tcells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.
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