Table 2.

Summary of NK cell subsets in non-alcoholic fatty liver disease.

Studies	Major Findings	Activation/Cytotoxicity	References
Murine NASH	Increased CD49b+ NKp46+NK cells. They play a role in polarizing Mϕ toward M1-like phenotypes.	Immunoregulatory depends on IFN-γ, but not granzyme	[89]
Human NAFLD	Decreased frequency of CD56 (dim)NK cells and MAIT cells in PBMC	Less NKG2D	[90]
Human and murine NAFLD	Adipose tissue NK cells (or ILC1-like cells) contribute to insulin resistance in mice express CD49a. However, no link between the presence and levels of adipose tissue CD49a+ NK cells and the presence of insulin resistance was noted in the investigated patients.	Adipose CD49a+ mixed ILC1s expressed the most IFN-γ, the least granzyme B, and no TRAIL, unlike ILC1s in liver.	[91,92,93]
Human NAFLD	NAFLD with F3-F4 fibrosis scores exhibited elevated levels of circulating cytotoxic CD56(dim)CD16(+) cells	Inhibition of NK activity correlated with decreased expression of insulin receptors. mTOR/ERK inhibition correlates with decreased CD56 dim insulin receptor expression and NK impairment.	[94]
Human NAFLD	NK cells were shown to have an important role in regulating liver fibrosis by directly killing activated hepatic stellate cells via the receptors NKG2D, NKp30 and TRAIL the p38/PI3K/AKT pathway	NK cells are activated by both cytokines, such as IL-12 and IL-18, and innate immune stimuli, such as ligation of TLRs. The secretion of IL-18 depends upon activation of the inflammasome, whereas TLRs are stimulated by microbial products.	[83]

NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; CD, co-receptor cluster of differentiation; NK, natural killer; ILC, innate lymphoid cells; MAIT, mucosal-associated invariant T; TLR, toll like receptor; IL, interleukin.