Myeloid cell-specific IL-4 receptor knockout partially protects from adipose tissue inflammation
| Autor: | Georg Brinker, Lilli Arndt, Constance Hobusch, Julia Braune, Nora Klöting, Jan Ackermann, Michaela Kirstein, Martin Gericke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Adipose tissue macrophages Immunology Macrophage polarization Adipose tissue Inflammation CD8-Positive T-Lymphocytes Diet High-Fat Proinflammatory cytokine Mice Internal medicine medicine Immunology and Allergy Macrophage Glucose homeostasis Animals Myeloid Cells Obesity Mice Knockout Chemistry Receptors Interleukin-4 Mice Inbred C57BL Endocrinology Glucose Adipose Tissue Interleukin-4 medicine.symptom Insulin Resistance Macrophage proliferation |
| Zdroj: | J. Immunol. 207, 3081-3089 (2021) |
| Popis: | 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 (IIl4raΔmyel) 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 IIl4raΔmyel 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, IIl4raΔmyel 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. |
| Databáze: | OpenAIRE |
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