Soluble mannose receptor induces proinflammatory macrophage activation and metaflammation | Zendy

Maria Embgenbroich | Zendy; Hendrik J.P. van der Zande | Zendy; Leonie Hussaarts | Zendy; Jonas Schulte-Schrepping | Zendy; Leonard R. Pelgrom | Zendy; Noemí GarcíaTardón | Zendy; Laura Schlautmann | Zendy; Isabel Stoetzel | Zendy; Kristian Händler | Zendy; Joost M. Lambooij | Zendy; Anna ZawistowskaDeniziak | Zendy; Lisa R. Hoving | Zendy; Karin de Ruiter | Zendy; Marjolein A. Wijngaarden | Zendy; Hanno Pijl | Zendy; Ko Willems van Dijk | Zendy; Bart Everts | Zendy; Vanessa van Harmelen | Zendy; Maria Yazdanbakhsh | Zendy; Joachim L. Schultze | Zendy; Bruno Guigas | Zendy; Sven Burgdorf | Zendy

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Soluble mannose receptor induces proinflammatory macrophage activation and metaflammation

Author(s) -

Maria Embgenbroich,

Hendrik J.P. van der Zande,

Leonie Hussaarts,

Jonas Schulte-Schrepping,

Leonard R. Pelgrom,

Noemí GarcíaTardón,

Laura Schlautmann,

Isabel Stoetzel,

Kristian Händler,

Joost M. Lambooij,

Anna ZawistowskaDeniziak,

Lisa R. Hoving,

Karin de Ruiter,

Marjolein A. Wijngaarden,

Hanno Pijl,

Ko Willems van Dijk,

Bart Everts,

Vanessa van Harmelen,

Maria Yazdanbakhsh,

Joachim L. Schultze,

Bruno Guigas,

Sven Burgdorf

Publication year - 2021

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.2103304118

Subject(s) - proinflammatory cytokine , macrophage , regulator , mannose receptor , receptor , downregulation and upregulation , homeostasis , immunology , inflammation , chemistry , microbiology and biotechnology , medicine , biology , biochemistry , in vitro , gene

Significance Obesity-associated metaflammation is an emerging disease, in which proinflammatory macrophages play a decisive role. Here, we identified the soluble mannose receptor (sMR) as a regulator of metaflammation and demonstrated increased levels of sMR in obese mice and humans. Additionally, we identified that increased sMR directly binds to CD45 on macrophages, inhibiting its activity and inducing inflammatory macrophage activation via the Akt/NF-κB pathway. Consequently, increased sMR levels induced inflammatory activation of metabolic tissue macrophages and aggravation of whole-body metabolic homeostasis. These data identify the MR as a regulator of macrophage activation and offer perspectives for therapeutic approaches for the treatment of metaflammation.

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