MG53 suppresses interferon-β and inflammation via regulation of ryanodine receptor-mediated intracellular calcium signaling.

Nature Communications
Matthew SermersheimJianjie Ma

Abstract

TRIM family proteins play integral roles in the innate immune response to virus infection. MG53 (TRIM72) is essential for cell membrane repair and is believed to be a muscle-specific TRIM protein. Here we show human macrophages express MG53, and MG53 protein expression is reduced following virus infection. Knockdown of MG53 in macrophages leads to increases in type I interferon (IFN) upon infection. MG53 knockout mice infected with influenza virus show comparable influenza virus titres to wild type mice, but display increased morbidity accompanied by more accumulation of CD45+ cells and elevation of IFNβ in the lung. We find that MG53 knockdown results in activation of NFκB signalling, which is linked to an increase in intracellular calcium oscillation mediated by ryanodine receptor (RyR). MG53 inhibits IFNβ induction in an RyR-dependent manner. This study establishes MG53 as a new target for control of virus-induced morbidity and tissue injury.

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Citations

Oct 9, 2020·American Journal of Respiratory and Critical Care Medicine·Adam D KenneyJacob S Yount
Nov 27, 2020·Frontiers in Physiology·Dathe Z Benissan-MessanPeter H U Lee
May 31, 2021·Current Opinion in Pharmacology·Bryan A WhitsonJianjie Ma

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Methods Mentioned

BETA
pull down
flow cytometry
ELISA
PCR
co-immunoprecipitation
immunoprecipitation
co-IP
PMA
enzyme-linked immunosorbent assay
transfection

Software Mentioned

CellSens Dimension
OLYMPUS
GraphPad Prism
ImageJ

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