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

Journal

CLINICAL IMMUNOLOGY
Volume 255, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2023.109744

Keywords

Obesity; NK cell; Cancer; Immunometabolism

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Natural killer (NK) cells play a critical role in protecting the body against infection and cancer by targeting infected or transformed cells and initiating immune responses. They also have a role in tissue homeostasis, including adipose tissue, where they control macrophage polarization and regulate stressed adipocyte fate. Obesity is associated with immune dysregulation, including defects in peripheral and adipose tissue NK cells, leading to increased rates of cancer and susceptibility to severe infections. This review summarizes the literature on NK cells in obesity, discussing the consequences, mechanisms, and therapeutic interventions.
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.

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