Potential impact of trained innate immunity on the pathophysiology of metabolic dysfunction-associated fatty liver disease.

Jannis Kountouras, Evangelos Kazakos, Stergios A Polyzos, Apostolis Papaefthymiou, Christos Zavos, Maria Tzitiridou-Chatzopoulou, Dimitrios Chatzopoulos, Elisabeth Vardaka, Anthia Gatopoulou, Foteini Kyrailidi, Maria C Mouratidou, Michael Doulberis

Journal: Clinical immunology (Orlando, Fla.) 2023;256():109776

PMID: 37742792

Full Text on Elsevier Science View on PubMed

Abstract

Metabolic dysfunction-associated fatty liver disease (MAFLD) occurs in a low-grade inflammatory milieu dependent on highly complex networks that span well-beyond the hepatic tissue injury. Dysfunctional systemic metabolism that characterizes the disease, is further induced in response to environmental cues that modify energy and metabolic cellular demands, thereby altering the availability of specific substrates that profoundly regulate, through epigenetic mechanisms, the phenotypic heterogeneity of immune cells and influence hematopoietic stem cell differentiation fate. This immuno-metabolic signaling drives the initiation of downstream effector pathways and results in the decompensation of hepatic homeostasis that precedes pro-fibrotic events. Recent evidence suggests that innate immune cells reside in different tissues in a memory effector state, a phenomenon termed trained immunity, that may be activated by subsequent exogenous (e.g., microbial, dietary) or endogenous (e.g., metabolic, apoptotic) stmuli. This process leads to long-term modifications in the epigenetic landscape that ultimately precondition the cells towards enhanced transcription of inflammatory mediators that accelerates MAFLD development and/or progression. In this mini review we aimed to present current evidence on the potential impact of trained immunity on the pathophysiology of MAFLD, shedding light on the complex immunobiology of the disease and providing novel potential therapeutic strategies to restrain the burden of the disease.

Address: Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Macedonia, Greece. Electronic address: [email protected].; Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Macedonia, Greece; Department of Midwifery, School of Healthcare Sciences, University of West Macedonia, Koila, Kozani 50100, Macedonia, Greece.; First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Macedonia, Greece.; Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Macedonia, Greece; First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Macedonia, Greece; Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London W1W 6DN, UK.; Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Macedonia, Greece.; Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Macedonia, Greece; Department of Nutritional Sciences and Dietetics, School of Health Sciences, International Hellenic University, Alexander Campus, 57400 Thessaloniki, Macedonia, Greece.; 2nd Department of Internal Medicine, General University Hospital of Alexandroupolis, Alexandroupolis, Greece.; Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 54642, Macedonia, Greece; First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Macedonia, Greece; Gastroklinik, Private Gastroenterological Practice, Horgen 8810, Switzerland; Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland.

DOI: 10.1016/j.clim.2023.109776

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MeSH Terms: Humans, Immunity, Innate, Trained Immunity, Immunologic Memory, Liver Diseases