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| Differentiation and immunosuppressive function of CD19+CD24hiCD27+ regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway |
| Jin-Yang Li a , b , c , # , Tian-Shuo Feng a , b , c , # , Ji Gao a , b , c , Xin-Xiang Yang a , b , c , Xiang-Cheng Li a , b , c , Zhen-Hua Deng a , b , c , Yong-Xiang Xia a , b , c , Zheng-Shan Wu a , b , c , ∗ |
a Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
b Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing 210029, China
c NHC Key Laboratory of Living Donor Liver Transplantation, Nanjing Medical University, Nanjing 210029, China
∗Corresponding author at: Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
E-mail address: wwzzss355@163.com (Z.-S. Wu).
# Contributed equally. |
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Abstract Background: Regulatory B cells (Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs (miRNAs), miR-29a-3p also inhibits translation by degrad- ing the target mRNA, and yet the relationship between Bregs and miR-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 (mBregs) 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 miR-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 mBregs in the circulating blood were significantly impaired. miR-29a-3p was found to be a regulator of mBregs 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 immuno- suppressive function of mBregs. The inhibition of miR-29a-3p in CD19+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into mBregs. In addition, the observed enhancement of differentiation and immunosuppressive function of mBregs upon miR-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells.
Conclusions: miR-29a-3p was found to be a crucial regulator for mBregs differentiation and immunosuppressive function. Silencing miR-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.
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2024, Vol. 23 
