Epigenetic reprogramming of hepatic antigen presenting cells in chronic liver disease

Chronic liver disease (CLD) is a high morbidity and mortality condition with a high incidence/prevalence worldwide. Despite the diverse etiological factors involved, common pathogenic hallmarks in CLD progression are the accumulation of scarring hepatic tissue and a sustained local and systemic inflammatory response. Considering the constant exposure of the liver to antigens and the delicate homeostatic immune surveillance that takes place in the organ, hepatic antigen presenting cells (hAPCs; i.e. Kupffer Cells, Liver Sinusoidal Endothelial Cells and Dendritic Cells) and their activity regulation are key players in the maintenance of intrahepatic immune tolerance. Epigenetic regulation is considered as a relevant mechanism in several stages of CLD development, currently recognized for playing a pivotal role in hepatic stellate cells activation in liver fibrosis as well as tumor suppressor gene silencing and tumoral microenvironment immune-escape. However, influence of epigenetic mechanisms over immune response in CLD continues under study. Here we comprehensively review the main epigenetic regulatory mechanisms controlling hAPCs regulation, considering the intricate crosstalk of epigenetic effectors and discussing recent studies supporting epigenetic interventions with promising therapeutical potential over inflammatory response during CLD progression.