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

Author

Listed:
  • Matthew Sermersheim

    (The Ohio State University Wexner Medical Center)

  • Adam D. Kenney

    (The Ohio State University Wexner Medical Center)

  • Pei-Hui Lin

    (The Ohio State University Wexner Medical Center)

  • Temet M. McMichael

    (The Ohio State University Wexner Medical Center)

  • Chuanxi Cai

    (The Ohio State University Wexner Medical Center)

  • Kristyn Gumpper

    (The Ohio State University Wexner Medical Center)

  • T. M. Ayodele Adesanya

    (The Ohio State University Wexner Medical Center)

  • Haichang Li

    (The Ohio State University Wexner Medical Center)

  • Xinyu Zhou

    (The Ohio State University Wexner Medical Center)

  • Ki-Ho Park

    (The Ohio State University Wexner Medical Center)

  • Jacob S. Yount

    (The Ohio State University Wexner Medical Center)

  • Jianjie Ma

    (The Ohio State University Wexner Medical Center)

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.

Suggested Citation

  • Matthew Sermersheim & Adam D. Kenney & Pei-Hui Lin & Temet M. McMichael & Chuanxi Cai & Kristyn Gumpper & T. M. Ayodele Adesanya & Haichang Li & Xinyu Zhou & Ki-Ho Park & Jacob S. Yount & Jianjie Ma, 2020. "MG53 suppresses interferon-β and inflammation via regulation of ryanodine receptor-mediated intracellular calcium signaling," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17177-6
    DOI: 10.1038/s41467-020-17177-6
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