Revisiting the Role of Natural Killer Cells in Non-Alcoholic Fatty Liver Disease

María Luz Martínez-Chantar,Teresa C Delgado,Naiara Beraza

doi:10.3389/fimmu.2021.640869

María Luz Martínez-Chantar, Teresa C Delgado + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2021.640869

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Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common form of chronic liver disease. The histological spectrum of NAFLD ranges from simple steatosis to chronic inflammation and liver fibrosis during Non-Alcoholic Steatohepatitis (NASH). The current view is that innate immune mechanisms represent a key element in supporting hepatic inflammation in NASH. Natural Killer (NK) cells are lymphoid cells and a component of the innate immune system known to be involved in NASH progression. Increasing evidence has shed light on the differential function of circulating and tissue-resident NK cells, as well as on the relevance of metabolism and the microenvironment in regulating their activity. Here, we revisit the complex role of NK cells as regulators of NASH progression as well as potential therapeutic approaches based on their modulation.

Highlights

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common form of chronic liver disease in western countries and affects over 25% of the population globally [1]
Alternative mechanisms contributing to the deleterious role of Natural Killer (NK) cells during Non-Alcoholic Steatohepatitis (NASH) include: the development of a “myeloid” phenotype of NK cells as these express high levels of CSF1 and CCR2 [40] (Figure 1); and induction of hepatic ER stress via osteopontin, which contributes to insulin resistance in the context of obesity [75]
Absence of IL-15 and IL-15Receptor alpha in KO mice associated with reduced steatosis that associated with lower inflammation during high-fat diet (HFD)-induced NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) [46]

Summary

Introduction

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common form of chronic liver disease in western countries and affects over 25% of the population globally [1]. Other studies described no changes in either frequency or absolute numbers of circulating CD56bright and CD56dim NK cells in obese, NAFL, or NASH patients [34, 40], and similar cytokine production and cytotoxic activity [34].

Results

Conclusion