Autophagy contributes to IL-17-induced plasma cell differentiation, in experimental autoimmune myocarditis

作者：Yuan, Jing; Yu, Miao; Li, Huan-Huan; Long, Qi; Liang, Wei; Wen, Shuang; Wang, Min; Guo, He-Ping; Cheng, Xiang^*; Liao, Yu-Hua

来源：International Immunopharmacology, 2014, 18(1): 98-105.

DOI：10.1016/j.intimp.2013.11.008

• Autophagy
• IL-17
• Plasma cells
• Apoptosis
• Experimental autoimmune myocarditis

Although IL-17 is considered to promote B cell differentiation into antibody-secreting plasma cells in some autoimmune diseases, its mechanism remains unclear. Recent studies revealed that autophagy, a lysosome-mediated catabolic process for providing nutrients under starvation, could regulate plasma cell homeostasis, so this study aimed to explore whether and how autophagy participates in IL-17-mediated plasma cell differentiation by MyHC-alpha-induced experimental autoimmune myocarditis (EAM) mouse model. It showed that IL-17 could not only induce B cell autophagy, but also facilitate the myocarditis severity, serum anti-MyHC-alpha autoantibody production and splenic CD38(+) CD138(+) B cell percentages, while the autophagy inhibitor 3-methyladenine attenuated these effects. Furthermore, serum anti-MyHC-alpha IgG autoantibody productions and CD38(+) CD138(+) B cell percentages were positively correlated with B cell autophagy levels respectively. In vitro, we further revealed that IL-17 could directly promote B cell autophagy, which boosted Blimp-1 expressions and CD38(+) CD138(+) B cell percentages. Moreover, elevated autophagy mediated by IL-17 enhanced ubiquitin-proteasome system activity and B cell anti-apoptotic ability by Beclin-1 and p62 through Erk1/2 phosphorylation, and these changes brought by IL-17 could be also inhibited with 3-methyladenine. Therefore, we concluded that autophagy contributed to IL-17-mediated plasma cell differentiation by regulating Blimp-1 expression and Bedin-l/p62 associated B cell apoptosis in EAM.

• 出版日期2014-1
• 单位华中科技大学