| First Author | Embgenbroich M | Year | 2021 |
| Journal | Proc Natl Acad Sci U S A | Volume | 118 |
| Issue | 31 | PubMed ID | 34326259 |
| Mgi Jnum | J:328903 | Mgi Id | MGI:6730993 |
| Doi | 10.1073/pnas.2103304118 | Citation | Embgenbroich M, et al. (2021) Soluble mannose receptor induces proinflammatory macrophage activation and metaflammation. Proc Natl Acad Sci U S A 118(31):e2103304118 |
| abstractText | Proinflammatory activation of macrophages in metabolic tissues is critically important in the induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor (sMR) plays a direct functional role in both macrophage activation and metaflammation. We show that sMR binds CD45 on macrophages and inhibits its phosphatase activity, leading to an Src/Akt/NF-kappaB-mediated cellular reprogramming toward an inflammatory phenotype both in vitro and in vivo. Remarkably, increased serum sMR levels were observed in obese mice and humans and directly correlated with body weight. Importantly, enhanced sMR levels increase serum proinflammatory cytokines, activate tissue macrophages, and promote insulin resistance. Altogether, our results reveal sMR as regulator of proinflammatory macrophage activation, which could constitute a therapeutic target for metaflammation and other hyperinflammatory diseases. |
