Pivotal Role of Dermal IL-17-Producing γδ T Cells in Skin Inflammation

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 T cells to produce IL-17 that led to disease progression. Dermal γδ T cells constitutively expressed the IL-23 receptor (IL-23R) and transcriptional factor RORγt. IL-17 production from dermal γδ T cells was independent of αβ T cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell 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 T cell expansion. In psoriasis patients, γδ T cells were greatly increased in affected skin and produced 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. [Display omitted] ► Dermal γδ T cells are the major source of IL-17 in the skin upon IL-23 stimulation ► Dermal γδ T cells have features with other IL-17-producing cells but also are unique ► γδ T cells are required for dermal inflammation and hyperplasia ► Dermal γδ T cells from human psoriatic skin are increased and produce IL-17