CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis.
CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis.
复制标题
DOI：
10.1038/ncomms9483
复制
发表时间：
2015-09-25
影响因子：
16.6
通讯作者：
Iwakura Y
中科院分区：
文献类型：
--
作者：
Murayama MA;Kakuta S;Inoue A;Umeda N;Yonezawa T;Maruhashi T;Tateishi K;Ishigame H;Yabe R;Ikeda S;Seno A;Chi HH;Hashiguchi Y;Kurata R;Tada T;Kubo S;Sato N;Liu Y;Hattori M;Saijo S;Matsushita M;Fujita T;Sumida T;Iwakura Y
补体系统对于宿主防御感染以及炎症性疾病的发展非常重要。在这里，我们发现 C1q/TNF 相关蛋白 6（CTRP6；基因符号 C1qtnf6）的表达在小鼠类风湿性关节炎 (RA) 模型中升高。由于补体激活增强，C1qtnf6−/− 小鼠对诱导性关节炎高度敏感，而 C1qtnf6 转基因小鼠则难治。阿图斯反应和实验性自身免疫性脑脊髓炎的发展在 C1qtnf6−/− 小鼠中也得到增强，并且 C1qtnf6−/− 胚胎是半致死的。我们发现 CTRP6 通过与 B 因子竞争 C3(H2O) 结合来特异性抑制补体系统的旁路途径。此外，通过关节内注射重组人CTRP6治疗关节炎诱发的小鼠可以治愈关节炎。 CTRP6 在人类滑膜细胞中表达，并且 RA 患者中 CTRP6 水平升高。这些结果表明CTRP6是一种内源性补体调节剂，可用于治疗补体介导的疾病。 补体系统会导致慢性炎症性疾病。在这里，作者表明 CRTP6 抑制补体旁路途径并逆转小鼠模型中的类风湿性关节炎。
The complement system is important for the host defence against infection as well as for the development of inflammatory diseases. Here we show that C1q/TNF-related protein 6 (CTRP6; gene symbol C1qtnf6) expression is elevated in mouse rheumatoid arthritis (RA) models. C1qtnf6−/− mice are highly susceptible to induced arthritis due to enhanced complement activation, whereas C1qtnf6-transgenic mice are refractory. The Arthus reaction and the development of experimental autoimmune encephalomyelitis are also enhanced in C1qtnf6−/− mice and C1qtnf6−/− embryos are semi-lethal. We find that CTRP6 specifically suppresses the alternative pathway of the complement system by competing with factor B for C3(H2O) binding. Furthermore, treatment of arthritis-induced mice with intra-articular injection of recombinant human CTRP6 cures the arthritis. CTRP6 is expressed in human synoviocytes, and CTRP6 levels are increased in RA patients. These results indicate that CTRP6 is an endogenous complement regulator and could be used for the treatment of complement-mediated diseases. The complement system contributes to chronic inflammatory diseases. Here the authors show that CRTP6 suppresses the alternative complement pathway and reverses rheumatoid arthritis in a mouse model of the disease.