Journal Article

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

Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Todorova, Dilyana, Simoncini, Stephanie, Lacroix, Romaric, Zaegel-Faucher, Olivia, Roll, Patrice, Assistance Publique - Hôpitaux de Marseille (APHM), Leroyer, Aurelie S, Balducci, Estelle, Lyonnet, Luc, Dignat-George, Francoise, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD) ; Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Poizot-Martin, Isabelle, Robert, Stephane, Chareyre, Corinne, Micallef, Joelle, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG) ; Aix M

2019

Overview

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.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK
• Subject: 13/109 / 631/80 / 631/80/86 / 82/51 / 82/80 / Adult / Animals / Antiretroviral agents / Antiretroviral therapy / Case-Control Studies / CD4 antigen / CD4-Positive T-Lymphocytes - cytology / CD4-Positive T-Lymphocytes - virology / Cell activation / Cell interactions / Cell Line / Endothelial cells / Endothelial Cells - chemistry / Endothelial Cells - cytology / Extracellular vesicles / Extracellular Vesicles - genetics / Female / Genetics / HIV / HIV Infections - genetics / HIV Infections - immunology / HIV-1 - immunology / HIV-1 - pathogenicity / Homeostasis / Human immunodeficiency virus / Human Umbilical Vein Endothelial Cells / Humanities and Social Sciences / Humans / Infectious diseases / Inflammation / Life Sciences / Lymphocytes / Lymphocytes T / Male / MicroRNAs / MicroRNAs - genetics / miRNA / multidisciplinary / Ribonuclease / Science / Science (multidisciplinary) / Up-Regulation
• ISBN: 0004755608000