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Sci Rep. 2019 Jul 16;9(1):10299. doi: 10.1038/s41598-019-44743-w.

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

Author information

1
Aix Marseille Univ, INSERM, C2VN, Marseille, France.
2
APHM, Hôpital La Conception, Laboratoire d'Hématologie et de biologie vasculaire, Marseille, France.
3
APHM, Hôpital Sainte-Marguerite, Service d'Immuno-hématologie clinique, Marseille, France.
4
APHM, Hôpital la Timone, Service de Pharmacologie, Marseille, France.
5
Aix Marseille Univ, CNRS, INT, Inst Neurosci Timone, Marseille, France.
6
Aix Marseille Univ, Inserm U912 (SESSTIM), Marseille, France.
7
Aix Marseille Univ, INSERM, MMG, Marseille, France.
8
APHM, Hôpital la Timone, Service de Biologie Cellulaire, Marseille, France.
9
Aix Marseille Univ, INSERM, C2VN, Marseille, France. francoise.dignat-george@univ-amu.fr.
10
APHM, Hôpital La Conception, Laboratoire d'Hématologie et de biologie vasculaire, Marseille, France. francoise.dignat-george@univ-amu.fr.

Abstract

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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