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Article Dans Une Revue Scientific Reports Année : 2019

Extracellular vesicles from T cells overexpress miR-146b-5p in HIV-1 infection and repress endothelial activation

Résumé

Human immunodeficiency virus type 1 (HIV-1) infection promotes a generalized activation of host responses that involves not only CD4 T cells, but also cells of the microenvironment, which are not directly infected, such as endothelial cells. The mechanisms triggering HIV-1-associated vascular alterations remain poorly understood. Extracellular vesicles (EVs), implicated in cell-to-cell communication, have been recently described as carriers of microRNAs (miRNAs). Here, we show that miR-146b-5p is upregulated in both CD4 T cells, CD4 T cell-derived EVs and circulating EVs obtained from antiretroviral therapy-naive HIV-1-infected patients. We further demonstrate that EVs from T cell line overexpressing miR-146b-5p mimics (miR-146b-EVs): 1) protect their miRNA cargo from RNase degradation, 2) transfer miR-146b-5p mimics into endothelial cells and 3) reduce endothelial inflammatory responses in vitro and in vivo in the lungs of mice through the downregulation of nuclear factor-κB-responsive molecules. These data advance our understanding on chronic inflammatory responses affecting endothelial homeostasis, in infectious and non-infectious diseases and pave the way for potential new anti-inflammatory strategies.

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Génétique
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hal-02478896 , version 1 (13-05-2020)

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Estelle Balducci, Aurelie S. Leroyer, Romaric Lacroix, Stephane Robert, Dilyana Todorova, et al.. Extracellular vesicles from T cells overexpress miR-146b-5p in HIV-1 infection and repress endothelial activation. Scientific Reports, 2019, 9 (10299), ⟨10.1038/s41598-019-44743-w⟩. ⟨hal-02478896⟩
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