Regulatory T cell activation, proliferation, and reprogramming induced by extracellular vesicles.
J Heart Lung Transplant
; 40(11): 1387-1395, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34281778
ABSTRACT
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 naïve 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 IL-10, and polarization toward an intermediate FOXP3+RORγt+ 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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
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Ativação Linfocitária
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Linfócitos T Reguladores
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Imunidade Adaptativa
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Vesículas Extracelulares
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Imunidade Inata
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Miocardite
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article