IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression

Abstract

Obesity is a primary risk factor for the development of non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common chronic liver disease in the world, represents a spectrum of disorders that range from steatosis (NAFL) to steatohepatitis (NASH) to cirrhosis. It is anticipated that NAFLD will soon surpass chronic hepatitis C infection as the leading cause for needing liver transplantation. Despite its clinical and public health significance no specific therapies are available. Although the etiology of NAFLD is multifactorial and remains largely enigmatic, it is well accepted that inflammation is a central component of NAFLD pathogenesis. Despite the significance, critical immune mediators, loci of immune activation, the immune signaling pathways and the mechanism(s) underlying disease progression remain incompletely understood. Recent findings have focused on the role of Interleukin 17 (IL-17) family of proinflammatory cytokines in obesity and pathogenesis of obesity-associated sequelae. Notably, obesity favors a Th17 bias and is associated with increased IL-17A expression in both humans and mice. Further, in mice, IL-17 axis has been implicated in regulation of both obesity and NAFLD pathogenesis. However, despite these recent advances several important questions require further evaluation including: the relevant cellular source of IL-17A production; the critical IL-17RA-expressing cell type; the critical liver infiltrating immune cells; and the underlying cellular effector mechanisms. Addressing these questions may aid in the identification and development of novel therapeutic targets for prevention of inflammation-driven NAFLD progression.

Microbiota, metabolome, and immune alterations in obese mice fed a high‐fat diet containing type 2 resistant starch

“…Previous studies have also shown a greater expression of antimicrobial peptides and TJP in response to a diet enriched with fermentable carbohydrates . Consistent with a protective effect of RS on the intestinal immune system was the reduced concentration of IL‐17A, a proinflammatory cytokine that is associated with risk for obesity‐related diseases .…”

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

“…In the liver, the IL-17 exacerbates the liver tissue inflammation (29, 105, 106), enhancing tissue leukocytes infiltration (107), is a mediator of the cross talk between the immune system and liver cells (85, 108–111), has a profibrotic effect as noted in liver biopsies (70, 85, 86), among several others effects. In addition, is a potent stimulator of production of other inflammatory mediators, such as tumor necrosis factor (TNF-α), interleukin-1 (IL-1), and IL-6 (85, 111, 112).…”

Relative and combined Effects of Ethanol and Hepatitis C Virus Infection on Serum Interleukin-17 Levels

“…The role of IL-17 in liver disease is still controversial [21]. Most studies have been performed among patients with nonalcoholic fatty liver disease (NAFLD).…”