IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell 
Subpopulation Deteriorates Energy and Glucose Homeostasis

Theurich, Sebastian; Tsaousidou, Eva; Hanssen, Ruth; Lempradl, Adelheid M.; Mauer, Jan; Timper, Katharina; Schilbach, Katharina; Folz-Donahue, Kat; Heilinger, Christian; Sexl, Veronika; Pospisilik, John Andrew; Wunderlich, F. Thomas; Brüning, Jens C.

doi:org/10.1016/j.cmet.2017.05.018

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IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis

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Lempradl, Adelheid M.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Pospisilik, John Andrew
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S155041311730342X
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Citation

Theurich, S., Tsaousidou, E., Hanssen, R., Lempradl, A. M., Mauer, J., Timper, K., et al. (2017). IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis. Cell Metabolism, 26, 171-184. doi:org/10.1016/j.cmet.2017.05.018.

Cite as: https://hdl.handle.net/21.11116/0000-0000-BF05-4

Abstract

Natural killer (NK) cells contribute to the development of obesity-associated insulin resistance. We demonstrate that in mice obesity promotes expansion of a distinct, interleukin-6 receptor (IL6R)a-expressing NK subpopulation, which also expresses a number of other myeloid lineage genes such as the colony-stimulating factor 1 receptor (Csf1r). Selective ablation of this Csf1r-expressing NK cell population prevents obesity and insulin resistance. Moreover, conditional inactivation of IL6Ra or Stat3 in NK cells limits obesity-associated formation of these myeloid signature NK cells, protecting from obesity, insulin resistance, and obesity-associated inflammation. Also in humans IL6Ra⁺ NK cells increase in obesity and correlate with markers of systemic low-grade inflammation, and their gene expression profile overlaps with characteristic gene sets of NK cells in obese mice. Collectively, we demonstrate that obesity-associated inflammation and metabolic disturbances depend on interleukin-6/Stat3-dependent formation of a distinct NK population, which may provide a target for the treatment of obesity, metaflammation-associated pathologies, and diabetes.