Hepatic Dendritic Cells in the Development and Progression of Metabolic Steatohepatitis

Abstract

Metabolic Associated Fatty liver disease (MAFLD) is a global health problem and represents the most common cause of chronic liver disease in the world. MAFLD spectrum goes from simple steatosis to cirrhosis, in between metabolic steatohepatitis with progressive fibrosis, which pathogenesis is not completely understood. Hence, the role of the immune system has become an important fact in the trigger of inflammatory cascades in metabolic steatohepatitis and in the activation of hepatic stellate cells (HSCs). Among, the more studied immune cells in the pathogenesis of MAFLD are macrophages, T cells, natural killer and dendritic cells. In particular, hepatic dendritic cells had recently attracted a special attention, with a dual role in the pathogenesis of MAFLD. These cells have the capacity to switch from a tolerant state to active state inducing an inflammatory cascade. Furthermore, these cells play a role in the lipid storage within the liver, having, thus providing a crucial nexus between inflammation and lipid metabolism. In this review, we will discuss the current knowledge on the dual role of dendritic cells in lipid accumulation, as wells as in the triggering of hepatic inflammation and hepatocytes cell death in metabolic steatohepatitis.

Peripheral immune cells in NAFLD patients: A spyhole to disease progression

“…As for DCs, although the role of DCs have not been vigorously explored in NAFLD-related basic studies, acquisition of proinflammatory capacity and enhanced lipid storage are two phenotypic changes found among hepatic dendritic cells in NAFLD microenvironment, indicating the potential important role of DCs in NAFLD pathogenesis. 83 Later researches on peripheral DCs in NAFLD patients mainly concentrate on the frequency changes in DC subsets, but the findings remain controversial. Haas et al found cDC2 frequency among PBMC was in significantly positive correlation with hepatocyte ballooning, while cDC1 frequency was not correlated with NAS score.…”

Analysis of Common Pathways and Markers From Non-Alcoholic Fatty Liver Disease to Immune-Mediated Diseases

“…This group of cells act as antigen-presenting cells in the liver, although their role is still under debate in NASH development, with contradictory preliminary results. These cells seem to play a role in the lipid storage within the liver, having migratory capacity, and are able to produce particular cytokines acting as a bridge between innate and adaptive processes ( 62 ).…”

Steatosis, Steatohepatitis and Cancer Immunotherapy: An Intricate Story

“…Specifically, adaptive immune response is directed either toward gut-derived antigens and neoantigens generated by free radical reaction with endogenous compounds (oxidative stress-derived epitopes, OSE). Remarkably, activated dendritic cells also accumulate lipids intracellularly and may, therefore, further promote lipotoxicity [ 84 , 85 ]. Adaptive immune responses are mediated by dendritic cell-mediated activation of CD4+ and CD8+ effector T lymphocytes which is finely modulated by the concomitant activation of regulatory T-cells (T reg ).…”

“…Anti-CTLA-4 monoclonal antibodies may disturb the activity of dendritic cells. Indeed, dendritic cells express the CTLA-4 receptors CD80/CD86, which are induced upon their switching to an activated phenotype and are involved in the activity of these cells in presenting antigens to T lymphocytes [ 85 , 90 ]. In addition, ICIs may alter Th1:Th17 and T reg cell number/activity [ 91 ].…”