論文 - 詳細
| RRC ID | 87877 |
|---|---|
| 著者 | Wang Y, Wang Y, Ding L, Ren X, Wang B, Wang L, Zhao S, Yue X, Wu Z, Li C, Liang X, Ma C, Gao L. |
| タイトル | Tim-4 reprograms cholesterol metabolism to suppress antiviral innate immunity by disturbing the Insig1-SCAP interaction in macrophages. |
| ジャーナル | Cell Rep |
| Abstract |
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. |
| 巻・号 | 41(9) |
| ページ | 111738 |
| 公開日 | 2022-11-29 |
| DOI | 10.1016/j.celrep.2022.111738 |
| PII | S2211-1247(22)01616-3 |
| PMID | 36450259 |
| MeSH | Cholesterol Immunity, Innate* Lipid Metabolism Macrophages |
| IF | 8.109 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | THP-1 |