title: Pivotal role of dermal IL-17-producing γδ T cells in skin inflammation.
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 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.
authors: Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 20025, PR China.
authors: Yihua
authors: Y
authors: Cai
authors: Xiaoyan
authors: X
authors: Shen
authors: Chuanlin
authors: C
authors: Ding
authors: Chunjian
authors: C
authors: Qi
authors: Kejia
authors: K
authors: Li
authors: Xia
authors: X
authors: Li
authors: Venkatakrishna R
authors: VR
authors: Jala
authors: Huang-ge
authors: HG
authors: Zhang
authors: Tian
authors: T
authors: Wang
authors: Jie
authors: J
authors: Zheng
authors: Jun
authors: J
authors: Yan
mesh_terms: D000818:Animals; D003872:Dermatitis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011565:Psoriasis / Q000276:immunology / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000276:immunology*; D053722:Receptors, Interleukin-17 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053722:Receptors, Interleukin-17