TGF-β-induced CD4+FoxP3+regulatory T cell-derived extracellular vesicles modulate Notch1 signaling through miR-449a and prevent collagen-induced arthritis in a murine model
作者机构：Department of Clinical ImmunologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Internal MedicineDivision of RheumatologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Division of RheumatologyDepartment of MedicinePenn State University Hershey Medical CenterHersheyPAUSA
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2021年第18卷第11期
页 面：2516-2529页
核心收录：
学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学]
基 金：This study was supported by the National Key R&D Program of China(2017YFA0105801) the General Program of the National Natural Science Foundation of China(81871224)
主 题：EVs iTreg Arthritis Th17 MicroRNA Notch1
摘 要：CD4^(+)FOXP3^(+)Treg cells are central to the maintenance of self-tolerance and can be defective in *** autoimmune rheumatic diseases,dysfunctional self-tolerance,is to a large extent,caused by insufficient Treg-cell *** nTregs have therapeutic effects in vivo,their relative scarcity and slow rate of in vitro expansion hinder the application of nTreg *** was previously reported that EVs contribute significantly to the suppressive function of FOXP3^(+)Treg *** that the stability and plasticity of nTregs remain major challenges in vivo,we established EVs derived from in vitro TGF-β-induced Treg cells(iTreg-EVs)and assessed their functions in a murine model of autoimmune *** results demonstrated that iTreg-EVs preferentially homed to the pathological joint and efficiently prevented the imbalance in Th17/Treg cells in arthritic ***,we found that miR-449a-5p mediated Notch1 expression modulation and that miR-449a-5p knockdown abolished the effects of iTreg-EVs on effector T cells and regulatory T cells in vitro and in *** together,our results show that iTreg-EVs control the inflammatory responses of recipient T cells through miR-449a-5p-dependent modulation of Notch1 and ameliorate the development and severity of arthritis,which may provide a potential cell-free strategy based on manipulating iTreg-EVs to prevent autoimmune arthritis.
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