| First Author | Ryu S | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 9 | Pages | 1609-1626.e7 |
| PubMed ID | 35963236 | Mgi Jnum | J:328359 |
| Mgi Id | MGI:7335896 | Doi | 10.1016/j.immuni.2022.07.007 |
| Citation | Ryu S, et al. (2022) The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity |
| abstractText | 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 2 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-beta, 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 health span 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. |
