| Literature DB >> 34326259 |
Maria Embgenbroich1, Hendrik J P van der Zande2, Leonie Hussaarts2, Jonas Schulte-Schrepping3, Leonard R Pelgrom2, Noemí García-Tardón2, Laura Schlautmann1, Isabel Stoetzel1, Kristian Händler4, Joost M Lambooij2, Anna Zawistowska-Deniziak2,5, Lisa Hoving6, Karin de Ruiter2, Marjolein Wijngaarden7, Hanno Pijl7, Ko Willems van Dijk6,7, Bart Everts2, Vanessa van Harmelen6, Maria Yazdanbakhsh2, Joachim L Schultze3,4, Bruno Guigas8, Sven Burgdorf9.
Abstract
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-κB-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.Entities:
Keywords: immunometabolism; macrophage; mannose receptor; metaflammation; obesity
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Year: 2021 PMID： 34326259 PMCID： PMC8346872 DOI： 10.1073/pnas.2103304118
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205