Autophagy contributes to IL-17-induced plasma cell differentiation in experimental autoimmune myocarditis
| Autor: | Xiang Cheng, Wei Liang, Yuhua Liao, Miao Yu, He-Ping Guo, Jing Yuan, Min Wang, Qi Long, Huan-Huan Li, Shuang Wen |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Plasma Cells Immunology Plasma cell Biology CD38 Autoimmune Diseases Mice Plasma cell differentiation Autophagy medicine Animals Immunology and Allergy Cells Cultured B cell Pharmacology B-Lymphocytes Mice Inbred BALB C Myosin Heavy Chains Adenine Interleukin-17 Cell Differentiation ADP-ribosyl Cyclase 1 Cell biology Myocarditis medicine.anatomical_structure Gene Expression Regulation Apoptosis Models Animal Beclin-1 Positive Regulatory Domain I-Binding Factor 1 Syndecan-1 Interleukin 17 Apoptosis Regulatory Proteins Homeostasis Transcription Factors |
| Zdroj: | International Immunopharmacology. 18:98-105 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2013.11.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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