Lymphocyte-activation gene 3+ (LAG3+) forkhead box protein 3- (FOXP3-) regulatory T cells induced by B cells alleviates joint inflammation in collagen-induced arthritis
Lymphocyte-activation gene 3+ (LAG3+) forkhead box protein 3- (FOXP3-) regulatory T cells induced by B cells alleviates joint inflammation in collagen-induced arthritis
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DOI：
10.1016/j.jaut.2016.02.002
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发表时间：
2016-04-01
影响因子：
12.8
通讯作者：
Chiang, Bor-Luen
中科院分区：
文献类型：
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作者：
Chen, Szu-Ying;Hsu, Wan-Tseng;Chiang, Bor-Luen
类风湿性关节炎（RA）是一种自身免疫性疾病，其中失调的免疫细胞主要针对滑膜关节。尽管最近在类风湿关节炎的治疗方面取得了进展，包括引入生物疗法和采用联合治疗疾病的抗风湿药物策略，但缓解率仍然不理想。先前的研究表明，诱导调节性T细胞（iTregs）的过继性转移对治疗小鼠胶原诱导关节炎（CIA）模型有效。本研究的目的是通过过继性转移LAG3(+) Treg-of-B细胞，开发基于itregg的CIA最佳潜在治疗方法。b细胞诱导的Treg-of-B细胞表达LAG3而不表达Foxp3（指定为LAG3(+) Treg-of-B），分泌IL-4、IL-10和tgf - β。此外，LAG3(+) Treg-of-B细胞通过LAG3和IL-10的产生抑制CD4(+)CD25（-）应答T细胞的增殖。在小鼠CIA模型中，LAG3(+) Treg-of-B细胞过继性转移减轻了关节严重程度以及局部和全身炎症。用LAG3(+) Treg-of-B细胞处理也能促进从脾脏和引流淋巴结分离的淋巴细胞产生IL-10。此外，接受LAG3(+) Treg-of-B细胞治疗的小鼠后足跖骨溶解明显减少，这与酒石酸盐抗性酸性磷酸酶表达下调有关。总之，我们确定了一个新的Tregs亚群用于CIA治疗。这一发现可能有助于探索新的基于调节性t细胞的人类自身免疫性疾病治疗方法。(C) 2016 Elsevier Ltd.版权所有。
Rheumatoid arthritis (RA) is an autoimmune disease in which dysregulated immune cells primarily target synovial joints. Despite recent advances in the treatment of RA, including the introduction of biologic therapies and employment of combination disease-modifying antirheumatic drug strategies, remission rates remain suboptimal. Previous studies have demonstrated that the adoptive transfer of induced regulatory T cells (iTregs) was effective in treating a murine model of collagen-induced arthritis (CIA). The objective of this study was to develop optimal potential iTreg-based therapy for CIA by adoptively transferring LAG3(+) Treg-of-B cells. B-cell-induced Treg-of-B cells expressed LAG3 but not Foxp3 (designated LAG3(+) Treg-of-B), and secreted IL-4, IL-10, and TGF-beta. Furthermore, LAG3(+) Treg-of-B cells suppressed the proliferation of CD4(+)CD25(-) responder T cells through both LAG3 and IL-10 production. In the murine CIA model, adoptive transfer of LAG3(+) Treg-of-B cells alleviated the joint severity as well as local and systemic inflammation. Treatment with LAG3(+) Treg-of-B cells also promoted IL-10 production in lymphocytes isolated from the spleen and draining lymph nodes. Moreover, mice receiving LAG3(+) Treg-of-B cell treatment showed significantly less pronounced osteolysis in the hind footpads, which correlated with the downregulation of tartrate-resistant acid phosphatase expression. In conclusion, we identified a novel subset of Tregs for CIA treatment. This insight may facilitate exploring novel regulatory T-cell-based therapies for human autoimmune diseases. (C) 2016 Elsevier Ltd. All rights reserved.