The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
In: Immunity, 2022
academicJournal
Zugriff:
The risk of chronic diseases caused by aging is reduced by caloric restriction (CR)-induced immunometabolic adaptation. Here, we found that the matricellular protein, secreted protein acidic and rich in cysteine (SPARC) was inhibited by two-years of 14% sustained CR in humans and elevated by obesity. SPARC converted anti-inflammatory macrophages into a pro-inflammatory phenotype with induction of interferon-stimulated gene (ISG) expression via the transcription factors IRF3/7. Mechanistically, SPARC-induced ISGs were dependent on toll-like receptor-4 (TLR4)-mediated TBK1, IRF3, IFN-β, and STAT1 signaling without engaging the Myd88 pathway. Metabolically, SPARC dampened mitochondrial respiration, and inhibition of glycolysis abrogated ISG induction by SPARC in macrophages. Furthermore, the N-terminal acidic domain of SPARC was required for ISG induction, while adipocyte-specific deletion of SPARC reduced inflammation and extended healthspan during aging. Collectively, SPARC, a CR-mimetic adipokine, is an immunometabolic checkpoint of inflammation and interferon response that may be targeted to delay age-related metabolic and functional decline.
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The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
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Autor/in / Beteiligte Person: | Ryu, Seungjin ; Sidorov, Sviatoslav ; Ravussin, Eric ; Artyomov, Maxim ; Iwasaki, Akiko ; Wang, Andrew ; Dixit, Vishwa Deep |
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Zeitschrift: | Immunity, 2022 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
DOI: | 10.1016/j.immuni.2022.07.007 |
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