Unraveling the Complex Interplay between Epigenetics and Immunity in Alcohol-Associated Liver Disease: A Comprehensive Review

Abstract

The mechanisms of immune dysfunction in alcohol-associated liver disease (ALD) have garnered growing research interest in recent times. Alcohol-mediated immune dysfunction has been implicated as a potential cause of ALD-associated microbial infection and inflammatory response. The immune microenvironment of an organism is essentially a complex network of interactions between immune cells, cytokines, extracellular matrix, and other immune-related molecules. This microenvironment is highly adaptive and responsive to environmental cues. Epigenetic reprogramming of the immune microenvironment has recently emerged as a key driver of ALD progression, particularly in the context of endotoxin tolerance and immune disorders. Although epigenetic modifications are known to play an important role in the regulation of the immune microenvironment in ALD, the specific mechanisms and molecular processes by which this regulation is achieved are yet to be fully understood. This paper aims to provide an overview of the current knowledge on the effects of alcohol consumption on epigenetics, with special focus on summarizing the data on the epigenetic regulatory mechanisms involved in the effects of alcohol consumption on the immune microenvironment. In addition, this paper aims to present a review of the epigenetic modifications involved in different forms of ALD. This review is expected to offer new perspectives for the diagnosis, treatment, monitoring, and prognostic assessment of ALD from an epigenetic perspective.

The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications

“…For example, it has demonstrated that the liver is a potential target of IL-19, IL-20, and IL-24 in the acute phase response [ 15 ]. Possible therapeutic approaches for the treatment of ALD could be the downregulation of IL-20 and the upregulation of IL-22 ratios through acquired epigenetic mechanisms [ 16 ]. Table 1 lists the roles of IL-20 subfamily members in liver diseases.…”

Alcohol-Associated Liver Disease Outcomes: Critical Mechanisms of Liver Injury Progression

“…Alcohol-induced changes in histone modification enzyme expression and activity affect multiple innate and adaptive immunity cell populations [36][37][38][39][40][41][42]. Alcohol-induced epigenetic changes were described for several types of immune cells (e.g., granulocytes, macrophages, and T-lymphocytes) and are thought to promote exaggerated inflammatory responses in ALD.…”

“…The roles of other histone modification enzymes and DNA methylation in immune cell phenotype were not specifically explored in ALD. However, the data from other disease models suggest that they could be implicated in altered cytokine production in macrophages and dendritic cells as well as altered CD8 + and CD4 + T cell phenotypes that promote liver injury and enhance alcohol-induced liver disease progression [37,40].…”