Natural Killer Cells as Sensors of Adipose Tissue Stress

Adipose tissue macrophages (ATMs) orchestrate low-grade chronic adipose tissue inflammation, linking obesity and insulin resistance. Whereas factors contributing to macrophage accumulation in adipose tissue are established, little is known regarding signals that link adipocyte stress to proinflammatory activation of macrophages. Natural killer (NK) cells are specialized innate lymphocytes that identify and respond to stressed cells. In this Opinion, we discuss the possibility of NK cells to function as sensors recognizing adipose tissue stress. We further summarize recent literature suggesting NK cells to play an important role in development of insulin resistance via secretion of cytokines that stimulate proinflammatory polarization of ATMs. This suggests adipose tissue-resident NK cells as a pharmacological target for the treatment of obesity-induced insulin resistance. Natural killer (NK) cells are innate lymphoid cells (ILCs) abundant in peripheral tissues that contribute to homeostatic processes. There is increasing evidence to link NK cells with metabolic homeostasis, dietary stress, and obesity.NK cells (and/or ILC1s) are professional sensors of cellular stress. In the obese state, NK cells accumulate in adipose tissue and sense tissue stress with ensuing activation and production of proinflammatory cytokines.NK cell-derived cytokines induce proinflammatory M1 macrophage polarization, subsequently leading to secretion of paracrine and endocrine factors that promotes insulin resistance.However, proinflammatory adipose tissue immune cells are not purely deleterious, as they also contribute to normal tissue homeostasis. This is important to consider when planning future anti-inflammatory therapeutic strategies targeting adipose tissue.