| First Author | Wang Y | Year | 2022 |
| Journal | Cell Rep | Volume | 41 |
| Issue | 9 | Pages | 111738 |
| PubMed ID | 36450259 | Mgi Jnum | J:331934 |
| Mgi Id | MGI:7407968 | Doi | 10.1016/j.celrep.2022.111738 |
| Citation | Wang Y, et al. (2022) Tim-4 reprograms cholesterol metabolism to suppress antiviral innate immunity by disturbing the Insig1-SCAP interaction in macrophages. Cell Rep 41(9):111738 |
| abstractText | Accumulating evidence indicates that macrophages reshape their cholesterol metabolism in response to pathogens to support host defense. Intervention of host cholesterol homeostasis has emerged as a promising strategy for antiviral therapy. T cell immunoglobulin and mucin domain-containing molecule 4 (Tim-4) is indispensable in maintaining the homeostasis of macrophages. However, its role in antiviral innate immunity and cholesterol metabolism remains unknown. Here, we report that Tim-4 deficiency results in boosted interferon (IFN) signaling and decreased viral load. Mechanistically, Tim-4 disturbs the Insig1-SCAP interaction and promotes SCAP-SREBP2 complex translocation to the Golgi apparatus, eventually leading to the upregulation of cholesterol biosynthesis in macrophages, which limits the type I IFN response. Our findings demonstrate that Tim-4 suppresses type I IFN signaling by enhancing SREBP2 activation, delineating the role of Tim-4 in antiviral innate immunity and cholesterol metabolism, which sheds light on the mechanism by which Tim-4 orchestrates macrophage homeostasis. |
