Abstract
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of liver disorders, from fatty liver to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Compared with fatty liver, NASH is characterized by increased liver injury and inflammation, in which liver-infiltrating immune cells, with neutrophil infiltration as a hallmark of NASH, play a critical role in promoting the progression of fatty liver to NASH. Neutrophils are the first responders to injury and infection in various tissues, establishing the first line of defense through multiple mechanisms such as phagocytosis, cytokine secretion, reactive oxygen species production, and neutrophil extracellular trap formation; however, their roles in the pathogenesis of NASH remain obscure. The current review summarizes the roles of neutrophils that facilitate the progression of fatty liver to NASH and their involvement in inflammation resolution during NASH pathogenesis. The notion that neutrophils are potential therapeutic targets for the treatment of NASH is also discussed.
Highlights
Neutrophils are the most populous subset of leukocytes in the circulation and participate in various processes of immune reactions and inflammation [1]
Because this review focuses on the role of neutrophils in nonalcoholic steatohepatitis (NASH) pathogenesis, this section highlights the inflammatory basis of the pathogenic events in NASH development and the link between lipotoxicity, hepatocyte injury, and inflammation
Knowledge on the role of neutrophils has rapidly expanded in recent years, which has enhanced our understanding of the pathogenic mechanism of NASH, and laid the foundation for its application in establishing an experimental NASH model that may be utilized for drug screening
Summary
Neutrophils are the most populous subset of leukocytes in the circulation and participate in various processes of immune reactions and inflammation [1]. With regard to sterile inflammation, neutrophils are activated and recruited to the site of injury as one of the first responders and participate in the inflammatory response to restore the physiological function of the tissue [3, 4]. Because of their versatile functions, neutrophils have been highlighted as a critical mediator of diseases in multiple organs, including the liver. The inflammatory properties of NASH are closely associated with the recruitment of innate immune cells, including neutrophils and monocytes; investigators have recently focused on the role of neutrophils in exacerbating inflammation and tissue damage during NASH development [11]. The current review discusses the protective function of neutrophils in NASH pathogenesis, which has recently gained attention [12]
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