MG53 suppresses interferon-β and inflammation via regulation of ryanodine receptor-mediated intracellular calcium signaling
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Nature communications - 11(2020), 1 vom: 17. Juli, Seite 3624 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sermersheim, Matthew [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.09.2020 Date Revised 09.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-020-17177-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312573642 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Kenney, Adam D |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Pei-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a McMichael, Temet M |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Chuanxi |e verfasserin |4 aut | |
| 700 | 1 | |a Gumpper, Kristyn |e verfasserin |4 aut | |
| 700 | 1 | |a Adesanya, T M Ayodele |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Haichang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Ki-Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Yount, Jacob S |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jianjie |e verfasserin |4 aut | |
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