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Macrophages in chronic liver failure: diversity, plasticity and therapeutic targeting

Title: Macrophages in chronic liver failure: diversity, plasticity and therapeutic targeting
Authors: Singanayagam, A
Triantafyllou, E
Item Type: Journal Article
Abstract: Chronic liver injury results in immune-driven progressive fibrosis, with risk of cirrhosis development and impact on morbidity and mortality. Persistent liver cell damage and death causes immune cell activation and inflammation. Patients with advanced cirrhosis additionally experience pathological bacterial translocation, exposure to microbial products and chronic engagement of the immune system. Bacterial infections have a high incidence in cirrhosis, with spontaneous bacterial peritonitis being the most common, while the subsequent systemic inflammation, organ failure and immune dysregulation increase the mortality risk. Tissue-resident and recruited macrophages play a central part in the development of inflammation and fibrosis progression. In the liver, adipose tissue, peritoneum and intestines, diverse macrophage populations exhibit great phenotypic and functional plasticity determined by their ontogeny, epigenetic programming and local microenvironment. These changes can, at different times, promote or ameliorate disease states and therefore represent potential targets for macrophage-directed therapies. In this review, we discuss the evidence for macrophage phenotypic and functional alterations in tissue compartments during the development and progression of chronic liver failure in different aetiologies and highlight the potential of macrophage modulation as a therapeutic strategy for liver disease.
Issue Date: 2-Apr-2021
Date of Acceptance: 18-Mar-2021
URI: http://hdl.handle.net/10044/1/88795
DOI: 10.3389/fimmu.2021.661182
ISSN: 1664-3224
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Immunology
Volume: 12
Copyright Statement: © 2021 Singanayagam and Triantafyllou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
cirrhosis
macrophages
liver injury
liver inflammation
liver fibrosis
chronic liver failure
Kupffer cells
Kupffer cells
chronic liver failure
cirrhosis
liver fibrosis
liver inflammation
liver injury
macrophages
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Article Number: ARTN 661182
Appears in Collections:Department of Metabolism, Digestion and Reproduction



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