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Epithelium- and endothelium-derived exosomes regulate the alveolar macrophages by targeting RGS1 mediated calcium signaling-dependent immune response
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Epithelium- and endothelium-derived exosomes regulate the alveolar macrophages by targeting RGS1 mediated calcium signaling-dependent immune response
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Journal Article
Epithelium- and endothelium-derived exosomes regulate the alveolar macrophages by targeting RGS1 mediated calcium signaling-dependent immune response
2021
Overview
Alveolar macrophages (AM) maintain airway immune balance; however, the regulation of heterogeneity of AMs is incompletely understood. We demonstrate that RGS1 coregulates the immunophenotype of AM subpopulations, including pro- and anti-inflammatory, injury- and repair-associated, and pro- and antifibrotic phenotypes, through the PLC-IP3R signal-dependent intracellular Ca
2+
response. Flt3
+
AMs and Tie2
+
AMs had different immune properties, and RGS1 expression in the cells was targeted by exosomes (EXOs) containing miR-223 and miR-27b-3p that were derived from vascular endothelial cells (EnCs) and type II alveolar epithelial cells (EpCs-II), respectively. Imbalance of AMs was correlated with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pulmonary fibrosis (PF) caused a lack of secretion of CD31
+
and CD74
+
EXOs derived from EnCs and EpCs-II. Timely treatment with EXOs significantly improved endotoxin-induced ALI/ARDS and bleomycin-induced PF in mice. Thus, EnC- and EpC-II-derived EXOs regulate the immune balance of AMs and can be used as potential therapeutic drugs.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/21
/ 13/31
/ 13/89
/ 14/19
/ 14/34
/ 38
/ 59
/ Acidosis
/ Acute Lung Injury - metabolism
/ Alveolar Epithelial Cells - physiology
/ Alveoli
/ Animals
/ Biomedical and Life Sciences
/ Calcium Signaling - immunology
/ E coli
/ Endothelial Cells - physiology
/ Exosomes
/ Fibrosis
/ Humans
/ Immunity
/ Inositol 1,4,5-trisphosphate receptors
/ Macrophages, Alveolar - metabolism
/ Mice
/ Proteins
/ Respiratory distress syndrome
/ Respiratory Distress Syndrome - metabolism
