Interleukin-6 signaling promotes alternative macrophage activation to limit obesity-associated insulin resistance and endotoxemia
By J. Mauer, Bhagirath Chaurasia, Julia Goldau, Merly C. Vogt, Johan Ruud, K. Nguyen, S. Theurich, A. C. Hausen, J. Schmitz, H. Brönneke and 8 more. Nature Immunology, 2014
600 citations recorded by the source corpus.
Obesity and resistance to insulin are closely associated with the development of low-grade inflammation. Interleukin 6 (IL-6) is linked to obesity-associated inflammation; however, its role in this context remains controversial. Here we found that mice with an inactivated gene encoding the IL-6Rα chain of the receptor for IL-6 in myeloid cells (Il6raΔmyel mice) developed exaggerated deterioration of glucose homeostasis during diet-induced obesity, due to enhanced resistance to insulin. Tissues targeted by insulin showed increased inflammation and a shift in macrophage polarization. IL-6 induced expression of the receptor for IL-4 and augmented the response to IL-4 in macrophages in a cell-autonomous manner. Il6raΔmyel mice were resistant to IL-4-mediated alternative polarization of macrophages and exhibited enhanced susceptibility to lipopolysaccharide (LPS)-induced endotoxemia. Our results identify signaling via IL-6 as an important determinant of the alternative activation of macrophages and assign an unexpected homeostatic role to IL-6 in limiting inflammation.
Subfields: Epidemiology, Immunology, Physiology
View Paper: https://www.semanticscholar.org/paper/4fea4beef70ac5f790b3c7cefca9b6b5bdf2b2ae
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Citations in the corpus
- Macrophage Polarization. (2017, background): “This pathway is regulated by STAT3 activation from the IL-10R or the IL-6R (40, 41).”
- Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020, unknown): “Studies in murine macrophages and hepatocytes show that IL-6 improves glucose homeostasis (109, 110).”