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

• DOI: 10.1016/j.intimp.2013.11.008
• Publication Date: 2013-11-21T22:12:18Z
• Authors: Jing Yuan; Miao Yu; Huan-Huan Li; Qi Long; Wei Liang; Shuang Wen; Min Wang; He-Ping Guo; Xiang Cheng; Yu-Hua Liao
• Keywords: Male; B-Lymphocytes; Mice, Inbred BALB C; 0303 health sciences; Myosin Heavy Chains; Adenine; Interleukin-17; Plasma Cells; Cell Differentiation; ADP-ribosyl Cyclase 1; Autoimmune Diseases; 3. Good health; Mice; Myocarditis; 03 medical and health sciences; Gene Expression Regulation; Models, Animal; Autophagy; Animals; Beclin-1; Positive Regulatory Domain I-Binding Factor 1; Apoptosis Regulatory Proteins; Cells, Cultured

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-α-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-α autoantibody production and splenic CD38(+) CD138(+) B cell percentages, while the autophagy inhibitor 3-methyladenine attenuated these effects. Furthermore, serum anti-MyHC-α 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 Beclin-1/p62 associated B cell apoptosis in EAM.