Differentiation and immunosuppressive function of CD19^(+)CD24^(hi)CD27^(+) regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway  

作　　者：Jin-Yang Li Tian-Shuo Feng Ji Gao Xin-Xiang Yang Xiang-Cheng Li Zhen-Hua Deng Yong-Xiang Xia Zheng-Shan Wu 

机构地区：[1]Hepatobiliary Center,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China [2]Key Laboratory of Liver Transplantation,Chinese Academy of Medical Sciences,Nanjing 210029,China [3]NHC Key Laboratory of Living Donor Liver Transplantation,Nanjing Medical University,Nanjing 210029,China

出　　处：《Hepatobiliary & Pancreatic Diseases International》2024年第5期472-480,共9页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (82070676);Jiangsu Provincial Medi-cal Innovation Center (CXZX202203);Jiangsu Provincial Medi-cal Key Laboratory (ZDXYS202201)。

摘　　要：Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

关 键 词：Regulatory B cells miR-29a-3p NFAT5 Liver transplantation 

分 类 号：R392.4[医药卫生—免疫学]