title: Autophagy contributes to IL-17-induced plasma cell differentiation in experimental autoimmune myocarditis.
abstract: 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.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Li
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wen
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Guo
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: nathancx@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: liaoyh27@126.com.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liao
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology*; D001343:Autophagy / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000071186:Beclin-1; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009205:Myocarditis / Q000276:immunology*; D018995:Myosin Heavy Chains / Q000276:immunology; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053668:Syndecan-1 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D020381:Interleukin-17; C513258:Prdm1 protein, mouse; D053668:Syndecan-1; D014157:Transcription Factors; C025946:3-methyladenine; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051997:ADP-ribosyl Cyclase 1; D018995:Myosin Heavy Chains; D000225:Adenine
keywords: Apoptosis; Autophagy; Experimental autoimmune myocarditis; IL-17; Plasma cells