Emerging Roles of T Cells in the Pathogenesis of Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. A significant proportion of patients with NAFLD develop a progressive inflammatory condition termed nonalcoholic steatohepatitis (NASH), which may eventually advance to cirrhosis and hepatocellular carcinoma (HCC). NASH is characterized by steatosis, hepatocyte ballooning, and lobular inflammation. Heightened immune cell infiltration is a hallmark of NASH, yet the mechanisms whereby hepatic inflammation occurs in NASH and how it contributes to disease initiation and progression remain incompletely understood. Emerging evidence indicates that intrahepatic T cell immune mechanisms play an integral role in the pathogenesis of NASH and its transition to HCC. In this review, we summarize the current knowledge regarding the T cell-mediated mechanisms of inflammation in NASH. We highlight recent preclinical and human studies implicating various subsets of conventional and innate-like T cells in the onset and progression of NASH and HCC. Finally, we discuss the potential therapeutic strategies targeting T cell-mediated responses for the treatment of NASH.

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits

“…The role of CD4+ T cells in NAFLD is less clear and studies using single-cell technologies will likely provide novel insights in the coming years. Numerous studies reported that Th1 and Th17 cells are elevated in patients with NASH [135]. Particularly, IFN-γ-expressing CD4 T cells were enriched in NASH and mice deficient in IFN-γ fed the MCD diet had milder steatohepatitis and J o u r n a l P r e -p r o o f reduced infiltration of inflammatory macrophages [136,137].…”

Bidirectional Association Between Psoriasis and Nonalcoholic Fatty Liver Disease: Real-World Evidence From Two Longitudinal Cohort Studies

“…Since Th17 lineage regulates metabolism and adipogenesis, proinflammatory cytokines could influence the onset of NAFLD ( 13 ). The major role of Th-17 lineage in liver were thought to be highly involved in the progression from NAFLD to the severe subtype of Nonalcoholic Steatohepatitis (NASH) ( 37 , 38 ). Additionally, abnormalities in visceral adipose tissue are considered to be involved in the pathogenesis of both diseases ( 14 ).…”

Hepatic damage caused by long-term high cholesterol intake induces a dysfunctional restorative macrophage population in experimental NASH

“…role: they can cross-communicate with neutrophils, natural killer cells, innate lymphoid cells, and lymphocytes, coordinating cell recruitment, activation, and subsequent fate of hepatic inflammation (29)(30)(31)(32).…”