Novel function of hydroxychloroquine: Down regulation of T follicular helper cells in collagen-induced arthritis
Novel function of hydroxychloroquine: Down regulation of T follicular helper cells in collagen-induced arthritis
复制标题
羟氯喹的新功能：在胶原诱导的关节炎中下调滤泡辅助 T 细胞
DOI：
10.1016/j.biopha.2017.10.132
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发表时间：
2018-01-01
影响因子：
7.5
通讯作者：
Sun, Erwei
中科院分区：
文献类型：
--
作者：
Han, Jiaochan;Zhou, Qingyou;Sun, Erwei
羟氯喹（HCQ）是一种广泛用于类风湿关节炎（RA）的免疫抑制剂。T滤泡辅助性（Tfh）细胞在类风湿关节炎的发病机制中起着至关重要的作用。然而，HCQ是否通过干扰Tfh细胞抑制关节炎的发展从未有过报道。为了解决这个问题，我们研究了新诊断的类风湿关节炎患者中Tfh细胞的百分比，发现其在外周血中上调。重要的是，在来自健康志愿者的外周血单个核细胞（PBMCs）的体外实验中，我们证明了在HCQ治疗后，PBMCs和纯化的CD4(+) T细胞中Tfh细胞的百分比降低。在胶原诱导性关节炎（CIA）模型的体内实验中，我们发现HCQ抑制了关节炎的发病率和评分，减少了血清中促炎细胞因子的分泌。与体外研究相似，HCQ治疗的CIA小鼠中Tfh细胞的比例下降到了赋形剂治疗组的水平。进一步的研究表明，HCQ抑制了由白细胞介素 - 12（IL - 12）和白细胞介素 - 21（IL - 21）刺激产生的Tfh细胞。总之，我们的研究表明了HCQ在类风湿关节炎中一种先前未被认识的机制，即HCQ可能通过阻断IL - 12和IL - 21信号通路直接抑制Tfh细胞的产生。
Hydroxychloroquine (HCQ) is an immunosuppressive agent widely used in rheumatoid arthritis (RA). T follicular helper (Tfh) cells play a vital role in the pathogenesis of RA. However, whether HCQ suppresses arthritis development through interfering with Tfh cells have never been reported. To address this issue, we investigated the percent of Tfh cells in newly diagnosed RA patients and found that they were up-regulated in peripheral blood. Importantly, in ex vivo experiments of peripheral blood mononuclear cells (PBMCs) from healthy volunteers, we proved that the percentage of Tfh cells in PBMCs and purified CD4(+) T cells were decreased after HCQ treatment. In in vivo experiments of collagen-induced arthritis (CIA) model, we discovered that HCQ suppressed the incidence and score of arthritis, reduced the secretion of proinflammatory cytokines in serum. Similar to ex vivo study, the ratio of Tfh cells in HCQ treated CIA mice declined to the level of vehicle-treated group. Further research demonstrated that HCQ inhibited the generation of Tfh cells stimulated by IL-12 and IL-21. In conclusion, our study indicates a previously unrecognized mechanism of HCQ in RA, that HCQ directly suppresses the generation of Tfh cells by blocking IL-12 and IL-21 signaling pathways probably.