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

21Citations
Citations of this article
60Readers
Mendeley users who have this article in their library.

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. A complex network of immune cells mediates obesity-associated low-grade inflammation. Theurich et al. describe a distinct, myeloid gene-expressing NK cell subpopulation that arises in obesity. Inhibition or depletion of this specific NK cell subpopulation decreases inflammation and protects from obesity and insulin resistance

Cite

CITATION STYLE

APA

Theurich, S., Tsaousidou, E., Hanssen, R., Lempradl, A. M., Mauer, J., Timper, K., … Brüning, J. C. (2017). IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis. Cell Metabolism, 26(1), 171-184.e6. https://doi.org/10.1016/j.cmet.2017.05.018

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free