NK cells vs. obesity: A tale of dysfunction & redemption

Natural killer (NK) cells are critical in protecting the body against infection and cancer. NK cells can rapidly respond to these threats by directly targeting the infected or transformed cell using their cytotoxic machinery or by initiating and amplifying the immune response via their production of cytokines. Additionally, NK cells are resident across many tissues including adipose, were their role extends from host protection to tissue homeostasis. Adipose resident NK cells can control macrophage polarization via cytokine production, whilst also regulating stressed adipocyte fate using their cytotoxic machinery. Obesity is strongly associated with increased rates of cancer and a heightened susceptibility to severe infections. This is in part due to significant obesity-related immune dysregulation, including defects in both peripheral and adipose tissue NK cells. In this review, we detail the literature to date on NK cells in the setting of obesity - outlining the consequences, mechanisms and therapeutic interventions.