RT Journal Article
SR Electronic
T1 MSC extracellular vesicles modulate human macrophages in ARDS towards anti-inflammatory phenotype via transfer of miRNA181-a and PTEN-pSTAT5-SOCS1 signalling
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP OA2695
DO 10.1183/13993003.congress-2021.OA2695
VO 58
IS suppl 65
A1 Yue Su
A1 David Simpson
A1 Cecilia O’Kane
A1 Derek Brazil
A1 Anna Krasnodembskaya
YR 2021
UL http://erj.ersjournals.com/content/58/suppl_65/OA2695.abstract
AB Background: Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are investigated as a novel therapy for ARDS, a better understanding of their mechanism of action is needed. Macrophages are important mediators of ARDS inflammatory response. Suppressor of Cytokine Signalling (SOCS) proteins are key regulators of macrophage phenotype switch.Aim: To investigate the role of SOCS1 protein in the EV modulation of macrophages.Hypothesis: EVs modulate SOCS1 via transfer of miRNA.Methods: human monocyte-derived macrophages (MDMs) were stimulated with LPS or ARDS plasma and treated with EVs. Protein expression was tested by Western blot. EV miR content was determined by MiRseq. Specific siRNAs, inhibitors, miR mimic were used to silence protein expression and to modulate expression of miR181a. In vivo: LPS-injured C57BL/6 mice were given EVs with and without miR181a.Results: EVs significantly reduced secretion of TNF-a and IL-8 by MDMs in the presence of LPS or ARDS plasma, effect was critically dependent on SOCS1. Transfer of miR181 in EVs downregulated PTEN and subsequently activated pSTAT5 leading to upregulation of SOCS1. In vivo EVs alleviated lung injury and upregulated pSTAT5 and SOCS1 in alveolar macrophages in a miR181-dependent manner.Conclusion: miRNA181a-PTEN-pSTAT5-SOCS1 is a novel pathway regulating inflammatory response in ARDS..FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA2695.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).