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Ackermann, J.* ; Arndt, L.* ; Kirstein, M.* ; Hobusch, C.* ; Brinker, G.* ; Klöting, N. ; Braune, J.* ; Gericke, M.*

Myeloid cell-specific IL-4 receptor knockout partially protects from adipose tissue inflammation.

J. Immunol. 207, 3081-3089 (2021)
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IL-4 receptor signaling is supposed to play a major role in anti-inflammatory polarization and proliferation of adipose tissue macrophages. In this study, we examined the metabolic and inflammatory phenotype of C57BL/6J mice (IIl4ra) with LysM-dependent knockout (IIl4ra Δmyel) of the IL-4 receptor α-chain (IL-4Rα), the mandatory signaling component of IL-4 and IL-13, on chow and high-fat diet. Lean IIl4ra Δmyel mice showed decreased insulin sensitivity, no divergent adipose tissue macrophage polarization, but an increased percentage of CD8+ T cells in visceral adipose tissue. After 20 wk of a high-fat diet, IIl4ra Δmyel mice exhibited higher glucose tolerance, no changes in the lymphocyte compartment and fewer M1 macrophages in visceral adipose tissue. In vivo adipose tissue macrophage proliferation measured by BrdU incorporation was unaffected by Il4ra knockout. Interestingly, we show that IL-4Rα signaling directly augmented Itgax (Cd11c) gene expression in bone marrow-derived macrophages and increased the amount of CD11c+ macrophages in adipose tissue explants. Myeloid cell-specific knockout of Il4ra deteriorated insulin sensitivity in lean mice but improved parameters of glucose homeostasis and partially protected from adipose tissue inflammation in obese mice. Hence, IL-4Rα signaling probably plays a minor role in maintaining the macrophage M2 population and proliferation rates in vivo. Moreover, our data indicate that IL-4 signaling plays a proinflammatory role in adipose tissue inflammation by directly upregulating CD11c on adipose tissue macrophages.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Necrosis-factor-alpha; Local Proliferation; Insulin-resistance; T-cells; Interleukin-4 Receptor; Obesity; Macrophages; Activation; Metabolism; Expression
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Journal Journal of Immunology
Quellenangaben Volume: 207, Issue: 12, Pages: 3081-3089 Article Number: , Supplement: ,
Publisher American Association of Immunologists
Publishing Place 9650 Rockville Pike, Bethesda, Md 20814 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants German Diabetes Association
German Research Center for Diabetes
Federal Ministry of Education and Research, Germany, IFB Adiposity Diseases
Deutsche Forschungsgemeinschaft
Federal Ministry of Education and Research, Germany, Integrated Research and Treatment Center (IFB) Adiposity Diseases
Deutsche Forschungsgemeinschaft (German Research Foundation)