CD30L/CD30 protects against psoriasiform skin inflammation by suppressing Th17-related cytokine production by V gamma 4( ) gamma delta T cells
CD30L/CD30 protects against psoriasiform skin inflammation by suppressing Th17-related cytokine production by V gamma 4( ) gamma delta T cells
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CD30L/CD30 通过抑制 V gamma 4( ) gamma delta T 细胞产生 Th17 相关细胞因子来预防银屑病皮肤炎症
DOI：
10.1016/j.jaut.2019.04.009
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发表时间：
2019
影响因子：
12.8
通讯作者：
Sun Xun
中科院分区：
文献类型：
--
作者：
Yue Dan;You Yong;Zhang Xiaoqing;Wang Biao;Wang Xiao;Qi Ruiqun;Yang Fan;Meng Xin;Yoshikai Yasunobu;Wang Yuanyuan;Sun Xun
银屑病是一种常见的自身免疫性慢性炎症性皮肤病。已经证明，皮肤T17细胞通过产生各种Th 17相关细胞因子在银屑病的发病机制中发挥重要的促炎作用。我们前期的研究表明，CD 30 L/CD 30信号在小鼠肠道相关淋巴组织中对CD 4 + Th 17细胞和Vγ6+γδ T17细胞的分化起着关键作用。然而，其对银屑病发病机制的影响尚不清楚。在这里，我们充分证明了CD 30 L/CD 30信号转导通过选择性抑制Vγ4+γδ T17细胞亚群中的CCR 6表达和Th 17相关细胞因子合成，在小鼠银屑病的发展中发挥新的保护作用。同时，用激动性抗CD 30 mAb治疗对我们的银屑病小鼠模型具有显著的治疗效果。因此，CD 30 L/CD 30信号通路是抗体治疗的理想靶点，有望成为银屑病免疫生物学治疗的新途径。
Psoriasis is a common, autoimmune, chronic inflammatory skin disease. It has been demonstrated that cutaneous T17 cells play an important pro-inflammatory role in the pathogenesis of psoriasis, through the production of various Th17-related cytokines. Our previous studies have demonstrated that CD30L/CD30 signal plays a pivotal role in the differentiation of CD4+Th17 cells and Vγ6+γδ T17 cells in the gut-associated lymphoid tissues of mouse. However, its effect on the pathogenesis of psoriasis is unknown. Here, we fully prove that CD30L/CD30 signaling plays a novel protective role in the development of psoriasis in mice, through selective inhibition of CCR6 expression and Th17-related cytokine synthesis in the Vγ4+γδ T17 cell subset. Meanwhile, treatment with agonistic anti-CD30 mAb had a significant therapeutic effect on our psoriasis mouse model. Therefore, the CD30L/CD30 signaling pathway is an ideal target for antibody therapy, which may become a new approach for the immunobiological treatment of psoriasis.