Published online Nov 7, 2016. doi: 10.3748/wjg.v22.i41.9096
Peer-review started: June 19, 2016
First decision: August 8, 2016
Revised: August 22, 2016
Accepted: September 14, 2016
Article in press: September 14, 2016
Published online: November 7, 2016
Processing time: 141 Days and 21.9 Hours
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.
Core tip: Interleukin-17 producing cells are important in maintaining inflammation since they are a source of pro-inflammatory cytokines and chemokines with a critical role in fighting extracellular bacteria. In the last years, this lymphocyte subset has been linked to the pathogenesis of multiple immune mediated diseases and in some cases to the progression to fibrosis. In this review, we discuss the role of the Th17 pathway in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis and to liver fibrosis analyzing previously published data obtained from different animal models and human studies of liver injury.