真皮IL-17中的γδT细胞在皮肤炎症中起着重要作用

2011-12-09 12:47 来源:丁香园 作者:上海交通大学医学院瑞金医院皮肤科
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Immunity 2011 Oct;35(4):596-610. [IF:24.221]

Pivotal Role of Dermal IL-17-Producing γδ T Cells in Skin Inflammation
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Cai Y , Shen X , Ding C , Qi C , Li K , Li X , Jala VR , Zhang HG , Wang T , Zheng J , Yan J .

Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 20025, P.R. China; Department of Medicine and Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.

美国肯塔基州癌症研究中心,上海交通大学医学院瑞金医院皮肤科,美国易斯维尔大学医学微生物学和免疫学系


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.

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