CD11cMHC2 Macrophages Are a New Inflammatory and Dynamic Subset in Murine Adipose Tissue

Overview

Journal Immunometabolism

Date 2022 Jan 6

PMID 34987865

Citations 1

Authors

Suzan Wetzels

Mitchell Bijnen

Erwin Wijnands

Jose van de Gaar

Andika Tan

Susan Coort

Erik A L Biessen

Casper G Schalkwijk

Kristiaan Wouters

Affiliations

Soon will be listed here.

Abstract

Background: The prevalence of obesity is rising and leads to increased morbidity and mortality. Adipose tissue inflammation, due to accumulation and activation of adipose tissue macrophages (ATMs), is a key driver of this phenomenon. Macrophages are heterogeneous cells, adapting quickly to the microenvironment, resulting in so-called M1 or M2 macrophages. In this study, we describe the dynamics and inflammatory properties of a newly identified ATM subset in obese mice.

Methods: LDLR mice received a high fat diet (HFD) for 5 weeks or 16 weeks to induce obesity. Adipose tissues were isolated and immune cell subsets were analyzed with flow cytometry or microarray analysis. Bone marrow transplantation (BMT) using CD45.1 and CD45.2 LDLR mice was performed to determine ATM origin.

Results: Upon HFD, there is a massive increase of ATM subsets in the adipose tissue. CD11cM2 ATMs could be subdivided based on their MHC2 expression into CD11cMHC2 ATMs and previously unidentified CD11cMHC2 ATMs. CD11cMHC2 ATMs accumulated very rapidly after 10 days of HFD, after which they increased even further with prolonged HFD. Microarray data showed that CD11cMHC2 ATMs resembled CD11cMHC2 ATMs in the steady state, but became more inflammatory during development of obesity. In vitro stimulation of bone marrow-derived macrophages with palmitate, abundantly present in HFD, resulted in the induction of the CD11cMHC2 phenotype.

Conclusions: Among M2 macrophages, a novel pro-inflammatory subset of macrophages was found based on their low level of MHC2 expression. This subset may play a role in the development of adipose tissue inflammation.

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