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

被引:892
作者
Cai, Yihua [1 ,2 ,3 ]
Shen, Xiaoyan [1 ]
Ding, Chuanlin [2 ,3 ]
Qi, Chunjian [2 ,3 ]
Li, Kejia [1 ]
Li, Xia [1 ]
Jala, Venkatakrishna R. [2 ,3 ]
Zhang, Huang-ge [2 ,3 ]
Wang, Tian [4 ]
Zheng, Jie [1 ]
Yan, Jun [2 ,3 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Dermatol, Shanghai 20025, Peoples R China
[2] Univ Louisville, Dept Microbiol & Immunol, James Graham Brown Canc Ctr, Louisville, KY 40202 USA
[3] Univ Louisville, Dept Med, James Graham Brown Canc Ctr, Louisville, KY 40202 USA
[4] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
基金
美国国家卫生研究院; 中国国家自然科学基金;
关键词
PSORIATIC SKIN; EPIDERMAL HYPERPLASIA; INTERFERON-GAMMA; INNATE IMMUNITY; IN-VITRO; EXPRESSION; RECEPTOR; INTERLEUKIN-17; IL-23; PATHOGENESIS;
D O I
10.1016/j.immuni.2011.08.001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 gamma delta T cells to produce IL-17 that led to disease progression. Dermal gamma delta T cells constitutively expressed the IL-23 receptor (IL-23R) and transcriptional factor ROR gamma t. IL-17 production from dermal gamma delta T cells was independent of alpha beta T cells. The epidermal hyperplasia and inflammation induced by IL-23 were significantly decreased in T cell receptor delta-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 gamma delta T cell expansion. In psoriasis patients, gamma delta T cells were greatly increased in affected skin and produced large amounts of IL-17. Thus, IL-23-responsive dermal gamma delta T cells are the major IL-17 producers in the skin and may represent a novel target for the treatment of psoriasis.
引用
收藏
页码:596 / 610
页数:15
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