Exosomes derived from microRNA-540-3p overexpressing mesenchymal stem cells promote immune tolerance via the CD74/nuclear factor-kappaB pathway in cardiac allograft  

作　　者：Ji-Gang He Xin-Xin Wu Si Li Dan Yan Gao-Peng Xiao Fu-Gang Mao 

机构地区：[1]Department of Cardiovascular Surgery,The First People’s Hospital of Yunnan Province,Kunming 650032,Yunnan Province,China [2]Yunnan University of Traditional Chinese Medicine,Kunming 650500,Yunnan Province,China [3]Department of Medical Intensive Care Unit,The First People’s Hospital of Yunnan Province,Kunming 650032,Yunnan Province,China [4]Department of Anaesthesia,The First People’s Hospital of Yunnan Province,Kunming 650032,Yunnan Province,China [5]Department of Ultrasonic,The First People’s Hospital of Yunnan Province,Kunming 650032,Yunnan Province,China

出　　处：《World Journal of Stem Cells》2024年第12期1022-1046,共25页世界干细胞杂志（英文）

基　　金：Supported by the National Natural Science Foundation of China,No.82060299;Medical Discipline Leader Project of Yunnan Provincial Health Commission,No.D-2019020;Yunnan Provincial Government Ten Thousand Person-Top Young Talents Project,No.KH-SWRQNBJ-2019-002;Clinical Medical Center of the First People’s Hospital of Yunnan Province,No.2021LCZXXF-XZ04 and No.2022LCZXKF-HX05;Kunming Medical Joint Special Project-Outstanding Youth Cultivation Project,No.202101AY070001-034;Kunming Medical Joint Special Project,No.202101AY070001-272;Famous Doctor Project of“Xingdian Talent Support Plan”of Yunnan Province,No.XDYC-MY-2022-0037;Yunnan Province 2023 Undergraduate Education and Teaching Reform Research Project,No.2023BKXJJG-F04002.

摘　　要：BACKGROUND Heart transplantation is a crucial intervention for severe heart failure,yet the challenge of organ rejection is significant.Bone marrow mesenchymal stem cells(BMSCs)and their exosomes have demonstrated potential in modulating T cells,dendtitic cells(DCs),and cytokines to achieve immunomodulatory effects.DCs,as key antigen-presenting cells,play a critical role in shaping immune responses by influencing T-cell activation and cytokine production.Through this modulation,BMSCs and their exosomes enhance graft tolerance and prolonging survival.AIM To explore the immunomodulatory effects of exosomes derived from BMSCs overexpressing microRNA-540-3p(miR-540-3p)on cardiac allograft tolerance,focusing on how these exosomes modulating DCs and T cells activity through the CD74/nuclear factor-kappaB(NF-κB)pathway.METHODS Rat models were used to assess the impact of miR-540-3p-enhanced exosomes on immune tolerance in cardiac allografts.MiR-540-3p expression was manipulated in BMSCs,and derived exosomes were collected and administered to the rat models post-heart transplantation.The study monitored expression levels of major histocompatibility complex II,CD80,CD86,and CD274 in DCs,and quantified CD4^(+)and CD8^(+)T cells,T regulatory cells,and cytokine profiles.RESULTS Exosomes from miR-540-3p-overexpressing BMSCs lead to reduced expression of immune activation markers CD74 and NF-κB p65 in DCs and T cells.Rats treated with these exosomes showed decreased inflammation and improved cardiac function,indicated by lower levels of pro-inflammatory cytokines(interleukin-1β,interferon-γ)and higher levels of anti-inflammatory cytokines(interleukin-10,transforming growth factorβ1).Additionally,miR-540-3p skewed the profiles of DCs and T cells towards immune tolerance,increasing the ratio of T regulatory cells and shifting cytokine secretion to favor graft acceptance.CONCLUSION Exosomes derived from BMSCs overexpressing miR-540-3p significantly enhance immune tolerance and prolong cardiac allograft survival by modulating

关 键 词：Bone marrow mesenchymal stem cells EXOSOMES MicroRNA-540-3p Cardiac allograft Immune tolerance 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]