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Review
. 2021 Feb 24:12:614429.
doi: 10.3389/fimmu.2021.614429. eCollection 2021.

Natural Killer Cells: Friend or Foe in Metabolic Diseases?

Yi Li  1   2   3 , Fangjie Wang  4 , Saber Imani  5 , Ling Tao  1 , Youcai Deng  6 , Yue Cai  1
Affiliations
Review

Natural Killer Cells: Friend or Foe in Metabolic Diseases?

Yi Li et al. Front Immunol. .

Abstract

The worldwide epidemic of metabolic diseases, especially obesity and other diseases caused by it, has shown a dramatic increase in incidence. A great deal of attention has been focused on the underlying mechanisms of these pathological processes and potential strategies to solve these problems. Chronic inflammation initiated by abdominal adipose tissues and immune cell activation in obesity is the major cause of the consequent development of complications. In addition to adipocytes, macrophages and monocytes, natural killer (NK) cells have been verified to be vital components involved in shaping the inflammatory microenvironment, thereby leading to various obesity-related metabolic diseases. Here, we provide an overview of the roles of NK cells and the interactions of these cells with other immune and nonimmune cells in the pathological processes of metabolic diseases. Finally, we also discuss potential therapeutic strategies targeting NK cells to treat metabolic diseases.

Keywords: atherosclerosis; insulin resistance; metabolic syndrome; natural killer cell; nonalcoholic fatty liver disease; obesity; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
NK cells participate in the inflammatory initiation of obesity-related diseases. In obesity, adipocytes tend to secrete MCP-1, recruiting more NK cells and monocyte/macrophages to infiltrate adipose tissues. Adipocytes also express ligands of NKp46 and NKG2D, which have not been specifically defined, to activate NK cells through signaling of surface-expressed activating receptors. Moreover, obesity promotes ATM polarization from an M2-like phenotype to an M1-like phenotype, which is a proinflammatory phenotype. M1-like ATMs secrete the chemokines MCP-1, CCL3, and CCL4 or cytokines IL-12 and IL-15, which also recruit NK cells and promote NK cell activation and proliferation. ATMs also express the NKG2D-specific ligand Rae-1. Activated NK cells in adipose tissue secrete inflammatory cytokines, such as IFN-γ and TNF-α, which also promote ATM polarization and activation. Finally, the large amounts of inflammatory cytokines produced by activated NK cells and ATMs in adipose tissue are released into the circulation, causing systemic inflammation and various metabolic diseases.
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