https://scholars.lib.ntu.edu.tw/handle/123456789/145225
標題: | Lymphocyte-activation gene 3(+) (LAG3(+)) forkhead box protein 3(-) (FOXP3(-)) regulatory T cells induced by B cells alleviates joint inflammation in collagen-induced arthritis | 作者: | Chen, Szu-Ying Hsu, Wan-Tseng Chen, Yi-Lien Chien, Chien-Hui Chiang, Bor-Luen |
關鍵字: | Lymphocyte-activation gene 3;Collagen-induced arthritis;Regulatory T cells;Rheumatoid arthritis | 公開日期: | 2016 | 期: | 68 | 起(迄)頁: | 75-85 | 來源出版物: | J. Autoimmun. | 摘要: | 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. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/278945 |
顯示於: | 臨床醫學研究所 |
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