Regulatory T cell activation, proliferation, and reprogramming induced by extracellular vesicles

被引：19

作者：

Akhmerov, Akbarshakh ^{[1
]}

Rogers, Russell ^{[1
]}

de Couto, Geoffrey ^{[1
]}

Valle, Jackelyn ^{[1
]}

Li, Liang ^{[1
]}

Ibrahim, Ahmed ^{[1
]}

Sanchez, Lizbeth ^{[1
]}

Zhang, Rui ^{[1
]}

Lin, Yen-Nien ^{[1
]}

Liu, Weixin ^{[1
]}

Marban, Eduardo ^{[1
]}

机构：

[1] Cedars Sinai Med Ctr, Smidt Heart Inst, 127 South San Vicente Blvd,AHSP A3600, Los Angeles, CA 90048 USA

来源：

JOURNAL OF HEART AND LUNG TRANSPLANTATION | 2021年 / 40卷 / 11期

基金：

美国国家卫生研究院;

关键词：

extracellular vesicles; regulatory T cells; CD4(+ )T cells; inflammation; CARDIOSPHERE-DERIVED CELLS; REGENERATION; LINEAGE; MOUSE; DIFFERENTIATION; MYOCARDITIS; EXPRESSION; EXOSOMES; EFFICACY; RECEPTOR;

D O I：

10.1016/j.healun.2021.06.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND: Extracellular vesicles (EVs) from heart stromal/progenitor cells modulate innate immunity, with salutary effects in a variety of cardiac disease models. Little is known, however, about the effects of these EVs on adaptive immunity. METHODS: Ex vivo differentiation of naive CD4+ T cells was conducted to assess the effect of EVs on cytokine production and proliferation of Th1, Th2, Th17, and regulatory T (Treg) cells. These effects were further tested in vivo using the experimental autoimmune myocarditis (EAM) model. RESULTS: Using differentiated CD4+ T cells, we show that EVs secreted by human-derived heart stromal/progenitor cells selectively influence the phenotype, activity, and proliferation of regulatory T (Treg) cells. Exposure of Treg cells to EVs results in faster proliferation, augmented production of IL10, and polarization toward an intermediate FOXP3+RORgt+ phenotype. In experimental autoimmune myocarditis, EVs attenuate cardiac inflammation and functional decline, in association with increased numbers of splenic IL10+-Treg cells. CONCLUSIONS: T cell modulation by EVs represents a novel therapeutic approach to inflammation, harnessing endogenous immunosuppressive mechanisms that may be applied in solid organ transplantation, graft-versus-host disease, and autoimmune disorders. J Heart Lung Transplant 2021;40:1387-1395 (c) 2021 International Society for Heart and Lung Transplantation. All rights reserved.

引用

页码：1387 / 1395

页数：9

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