Immune complex negatively regulates Toll-like receptor 9-mediated immune responses in B cells through the inhibitory Fc-gamma receptor IIb
Immune complex negatively regulates Toll-like receptor 9-mediated immune responses in B cells through the inhibitory Fc-gamma receptor IIb
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免疫复合物通过抑制性 Fc-gamma 受体 IIb 负向调节 B 细胞中 Toll 样受体 9 介导的免疫反应
DOI：
10.1111/1348-0421.12224
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发表时间：
2015
影响因子：
2.6
通讯作者：
Ji Mingchun
中科院分区：
文献类型：
--
作者：
Qian Li;Chen Wenyan;Qin Hongchao;Rui Chenglei;Jia Xiaoqin;Fu Yi;Gong Weijuan;Tian Fang;Ji Mingchun
由于Toll样受体9（TLR 9）的不适当激活可诱导病理损伤，因此TLR 9触发的免疫应答的负调节引起了相当大的关注。非致病性免疫复合物（IC）已被证明在某些自身免疫性疾病中具有有益的治疗作用。然而，IC在调节TLR 9触发的免疫应答中的作用及其潜在机制仍不清楚。在这项研究中，证明了B细胞的IC刺激不仅抑制了CpG-寡脱氧核苷酸（CpG-ODN）诱导的促炎性IL-6和IgM κ的产生，而且还减弱了CD 40和CD 80的表达。此外，我们的结果表明，IgG（FcγR）IIb的Fc部分的受体参与IC对TLR 9介导的CD 40、CD 80和IL-6表达的抑制作用。最后，发现IC下调CpG‐ODN激活的B细胞中的TLR 9表达。我们的研究结果提供了一个新的途径，通过FcγRIIb在B细胞中负调控TLR 9触发的免疫应答。为非致病性IC对炎症和自身免疫性疾病的治疗作用提供了新的机制解释。
Because inappropriate activation of Toll‐like receptor 9 (TLR9) may induce pathological damage, negative regulation of the TLR9‐triggered immune response has attracted considerable attention. Nonpathogenic immune complex (IC) has been demonstrated to have beneficial therapeutic effects in some kinds of autoimmune diseases. However, the role of IC in the regulation of TLR9‐triggered immune responses and the underlying mechanisms remain unclear. In this study, it was demonstrated that IC stimulation of B cells not only suppresses CpG‐oligodeoxynucleotide (CpG‐ODN)‐induced pro‐inflammatory IL‐6 and IgM κ production, but also attenuates CD40 and CD80 expression. Furthermore, our results suggest that the receptor for the Fc portion of IgG (FcγR) IIb is involved in the suppressive effect of IC on TLR9‐mediated CD40, CD80 and IL‐6 expression. Finally, it was found that IC down‐regulates TLR9 expression in CpG‐ODN activated B cells. Our results provide an outline of a new pathway for the negative regulation of TLR9‐triggered immune responses in B cells via FcγRIIb. A new mechanistic explanation of the therapeutic effect of nonpathogenic IC on inflammatory and autoimmune diseases is also provided.