Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response.
Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response.
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程序 Death-1 通过抑制 Th17 反应来抑制自身免疫性关节炎。
DOI：
10.1007/s00005-016-0404-z
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发表时间：
2016
影响因子：
3.2
通讯作者：
Zhang,Jian
中科院分区：
文献类型：
--
作者：
Yang,Lifen;Qiao,Guilin;Hassan,Yassir;Li,Zhenping;Zhang,Xiaoqing;Kong,Huimin;Zeng,Weimin;Yin,Fei;Zhang,Jian
程序性死亡-1(PD-1)是一种共抑制受体，可在活化的T细胞上诱导表达。PD-1已被报道与包括类风湿性关节炎在内的多种自身免疫性疾病的发生有关，但其确切的细胞和分子机制尚未完全阐明。为了研究PD-1在类风湿关节炎发病机制中的作用及其可能的机制，我们对C57BL/6小鼠进行了胶原诱导性关节炎(CIA)实验。在这里，我们表明PD-1缺乏导致严重的CIA在小鼠中的发展。在体外分析CIA小鼠的T细胞时，我们注意到缺乏PD-1的小鼠出现了异常的抗原特异性Th17反应。这可能是由于PKC-θ和Akt的非调控激活所致。为了支持这一观点，给Pdcd1−/−小鼠使用PI3-θ和Akt上游的PI3-Kinase抑制剂显著抑制了疾病的严重性。因此，我们的数据表明，PD-1抑制抗原特异性的Th17反应，从而抑制疾病。
Program death-1 (PD-1) is a co-inhibitory receptor inducibly expressed on activated T cells. PD-1 has been reported to be associated with the development of several autoimmune diseases including rheumatoid arthritis, but the precise cellular and molecular mechanisms have not been fully elucidated. To study the role of PD-1 in the pathogenesis of rheumatoid arthritis and the possible underlying mechanisms, we performed collagen-induced arthritis (CIA) in C57BL/6 mice. Here, we show that PD-1 deficiency leads to the development of severe CIA in mice. When analyzing T cells from CIA mice ex vivo, we noticed aberrant antigen-specific Th17 responses in mice lacking PD-1. This is possibly due to deregulated activation of PKC-θ and Akt. In support of this notion, treatingPdcd1−/−mice with an inhibitor of PI3-kinase that is upstream of PKC-θ and Akt significantly suppressed the disease severity. Therefore, our data indicate that PD-1 dampens antigen-specific Th17 response, thus inhibiting the disease.