IL-10-Producing Regulatory B10 Cells Ameliorate Collagen-Induced Arthritis via Suppressing Th17 Cell Generation
IL-10-Producing Regulatory B10 Cells Ameliorate Collagen-Induced Arthritis via Suppressing Th17 Cell Generation
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DOI：
10.1016/j.ajpath.2012.03.010
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发表时间：
2012-06-01
影响因子：
6
通讯作者：
Lu, Liwei
中科院分区：
文献类型：
--
作者：
Yang, Min;Deng, Jun;Lu, Liwei
产生IL-10的CD1d(h)lCD5(+) B细胞，也称为B10细胞，已被证明具有抑制免疫反应的调节功能，但B10细胞是否以及如何抑制自身免疫性关节炎的发展仍不清楚。在这项研究中，我们检测到与佐剂治疗的对照小鼠相比，在胶原诱导性关节炎（CIA）急性期，小鼠脾脏和引流淋巴结中产生IL-10的B细胞数量显着减少，但产生IL-17的CD4（+）T（Th17）细胞数量增加。在体外扩增的 B10 细胞过继转移中，胶原蛋白免疫小鼠的关节炎发病明显延迟，临床症状和关节损伤的严重程度减轻，同时 Th17 细胞数量大幅减少。为了确定B10细胞是否直接抑制培养中Th17细胞的产生，将用羧基荧光素琥珀酰亚胺酯（CFSE）标记的幼稚CD4（+）T细胞与B10细胞共培养。这些 B10 细胞通过减少 STAT3 磷酸化和视黄醇相关孤儿受体 gamma t (ROR gamma t) 表达来抑制 Th17 细胞分化。此外，当与 B10 细胞共培养时，11117 细胞的增殖显着降低。尽管Th17细胞的过继转移引发了IL-17(-/-)DBA/1J小鼠中胶原诱导的关节炎的发生，但B10细胞与Th17细胞的共同转移极大地延迟了关节炎的发病。因此，我们的研究结果表明 B10 细胞通过抑制 Th17 细胞生成在关节炎进展中发挥新的调节作用。 （Am J Pathol 2012 年，180：2375-2385；http://dx.doi.org/10.1016/j.ajpath.2012.03.010）
IL-10-producing CD1d(h)lCD5(+) B cells, also known as B10 cells, have been shown to possess a regulatory function in the inhibition of immune responses, but whether and how B10 cells suppress the development of autoimmune arthritis remain largely unclear. In this study, we detected significantly decreased numbers of IL-10-producing B cells, but increased IL-17-producing CD4(+) T (Th17) cells in both spleen and draining lymph nodes of mice during the acute stage of collagen-induced arthritis (CIA) when compared with adjuvant-treated control mice. On adoptive transfer of in vitro expanded B10 cells, collagen-immunized mice showed a marked delay of arthritis onset with reduced severity of both clinical symptoms and joint damage, accompanied by a substantial reduction in the number of Th17 cells. To determine whether B10 cells directly inhibit the generation of Th17 cells in culture, naive CD4(+) T cells labeled with carboxyfiuorescein succinimidyl ester (CFSE) were co-cultured with B10 cells. These B10 cells suppressed Th17 cell differentiation via the reduction of STAT3 phosphorylation and retinoid-related orphan receptor gamma t (ROR gamma t) expression. Moreover, 11117 cells showed significantly decreased proliferation when co-cultured with B10 cells. Although adoptive transfer of Th17 cells triggered the development of collagen-induced arthritis in IL-17(-/-)DBA/1J mice, co-transfer of B10 cells with Th17 cells profoundly delayed the onset of arthritis. Thus, our findings suggest a novel regulatory role of B10 cells in arthritic progression via the suppression of Th17 cell generation. (Am J Pathol 2012, 180:2375-2385; http://dx.doi.org/10.1016/j.ajpath.2012.03.010)