Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis

Abstract

The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis. During the last years, Th17 cells have been involved in the development of inflammation not only in liver but also in other organs, such as adipose tissue or lung. Differentiation of a naïve T cell into a Th17 cell leads to pro-inflammatory cytokine and chemokine production with subsequent myeloid cell recruitment to the inflamed tissue. Th17 response can be mitigated by T regulatory cells that secrete anti-inflammatory cytokines. Both T cell subsets need TGF-β for their differentiation and a characteristic plasticity in their phenotype may render them new therapeutic targets. In this review, we discuss the role of the Th17 pathway in NAFLD progression to NASH and to liver fibrosis analyzing different animal models of liver injury and human studies.

GWAS and enrichment analyses of non-alcoholic fatty liver disease identify new trait-associated genes and pathways across eMERGE Network

“…IL-17RA is ubiquitously expressed on a wide range of tissues (liver, intestine, lung, adipose tissue) and cell types (endothelial and immune cells). Indeed, previous published findings clearly established that the IL-17 axis plays an important role in NAFLD pathogenesis in multiple NAFLD murine models [58][59][60] including a role in a recently described, more human-like experimental model of NAFLD [61]. Notably, our novel data reinforce these findings in humans with a promising novel genetic biomarker (rs5748926, see Additional file 1: Table S4).…”

A long‐acting FGF21 alleviates hepatic steatosis and inflammation in a mouse model of non‐alcoholic steatohepatitis partly through an FGF21‐adiponectin‐IL17A pathway

“…We chose the CD-HFD-induced NASH mouse model because the metabolic characteristics of this model more closely resemble those of human NASH (Wolf et al, 2014;Chackelevicius et al, 2016) and this model provides measurements of a broader range of relevant metabolic parameters than those available for CD or MCD dietinduced NASH.…”

Immune and Inflammatory Pathways in Non-Alcoholic Steatohepatitis (NASH). An update

“…NASH is a disease considered to be the liver manifestation of the metabolic syndrome (MS) (1). Its incidence and prevalence are continually increasing worldwide.…”