Pivotal Role of Dermal IL-17-Producing γδ T Cells in Skin Inflammation
Immunity, Volume 35, Issue 4, 596-610, 06 October 2011
Copyright © 2011 Elsevier Inc. All rights reserved.
10.1016/j.immuni.2011.08.001Referred to by: An erratum has been published for this articleAuthors
Yihua Cai,Xiaoyan Shen,Chuanlin Ding,Chunjian Qi,Kejia Li,Xia Li,Venkatakrishna R. Jala,Huang-ge Zhang,Tian Wang,Jie Zheng
,Jun YanSee AffiliationsSummary
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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Copyright © 2011 Elsevier Inc. All rights reserved.
10.1016/j.immuni.2011.08.001
,Jun YanSee AffiliationsSummary
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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