Bai Ying, Liu Ruolan, Huang DeRen, La Cava Antonio, Tang Yi-yuan, Iwakura Yoichiro, Campagnolo Denise I, Vollmer Timothy L, Ransohoff Richard M, Shi Fu-Dong
Institute of Neuroinformatics and Laboratory for Brain and Mind, Dalian University of Technology, Dalian, China.
Eur J Immunol. 2008 Jul;38(7):1877-88. doi: 10.1002/eji.200737973.
The development and function of Th17 cells are influenced in part by the cytokines TGF-beta, IL-23 and IL-6, but the mechanisms that govern recruitment and activity of Th17 cells during initiation of autoimmunity remain poorly defined. We show here that the development of autoreactive Th17 cells in secondary lymphoid organs in experimental autoimmune myasthenia gravis--an animal model of human myasthenia gravis--is modulated by IL-6-producing CD11b(+) cells via the CC chemokine ligand 2 (CCL2). Notably, acetylcholine receptor (AChR)-reactive Th17 cells provide help for the B cells to produce anti-AChR antibodies, which are responsible for the impairment of the neuromuscular transmission that contributes to the clinical manifestations of autoimmunity, as indicated by a lack of disease induction in IL-17-deficient mice. Thus, Th17 cells can promote humoral autoimmunity via a novel mechanism that involves CCL2.
Th17细胞的发育和功能部分受细胞因子转化生长因子-β、白细胞介素-23和白细胞介素-6的影响，但在自身免疫起始过程中调控Th17细胞募集和活性的机制仍不清楚。我们在此表明，在实验性自身免疫性重症肌无力（一种人类重症肌无力的动物模型）的次级淋巴器官中，自身反应性Th17细胞的发育受产生白细胞介素-6的CD11b(+)细胞通过CC趋化因子配体2（CCL2）的调节。值得注意的是，乙酰胆碱受体（AChR）反应性Th17细胞为B细胞产生抗AChR抗体提供帮助，这些抗体导致神经肌肉传递受损，从而导致自身免疫的临床表现，这在白细胞介素-17缺陷小鼠中缺乏疾病诱导得到证明。因此，Th17细胞可通过一种涉及CCL2的新机制促进体液自身免疫。
Zotero 插件