Macrophage Polarization and Its Role in Liver Disease

Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) u...

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Published in	Frontiers in immunology Vol. 12; p. 803037
Main Authors	Wang, Cheng, Ma, Cheng, Gong, Lihong, Guo, Yuqin, Fu, Ke, Zhang, Yafang, Zhou, Honglin, Li, Yunxia
Format	Journal Article
Language	English
Published	Switzerland Frontiers Media S.A 14.12.2021
Subjects	acute liver injury alcoholic liver disease Animals Biomarkers Cell Differentiation Cell Plasticity - genetics Cell Plasticity - immunology Diagnosis, Differential Disease Susceptibility - immunology Energy Metabolism Gene Expression Regulation Humans Immunology liver disease Liver Diseases - diagnosis Liver Diseases - etiology Liver Diseases - metabolism Liver Diseases - therapy Macrophage Activation - genetics Macrophage Activation - immunology macrophage polarization Macrophages - immunology Macrophages - metabolism Macrophages - pathology metabolic-associated fatty liver disease Organ Specificity - genetics Organ Specificity - immunology Phenotype Signal Transduction viral hepatitis viral hepatitis alcoholic liver disease liver fibrosis liver disease macrophage polarization metabolic-associated fatty liver disease hepatocellular carcinoma acute liver injury
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Abstract	Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus playing different roles and functions. Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic liver disease, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Recent studies have shown that macrophage polarization plays an important role in the initiation and development of liver diseases. However, because both macrophage polarization and the pathogenesis of liver diseases are complex, the role and mechanism of macrophage polarization in liver diseases need to be further clarified. Therefore, the origin of hepatic macrophages, and the phenotypes and mechanisms of macrophage polarization are reviewed first in this paper. It is found that macrophage polarization involves several molecular mechanisms, mainly including TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, and miRNA signaling pathways. In addition, this paper also expounds the role and mechanism of macrophage polarization in various liver diseases, which aims to provide references for further research of macrophage polarization in liver diseases, contributing to the therapeutic strategy of ameliorating liver diseases by modulating macrophage polarization.
AbstractList	Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus playing different roles and functions. Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic liver disease, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Recent studies have shown that macrophage polarization plays an important role in the initiation and development of liver diseases. However, because both macrophage polarization and the pathogenesis of liver diseases are complex, the role and mechanism of macrophage polarization in liver diseases need to be further clarified. Therefore, the origin of hepatic macrophages, and the phenotypes and mechanisms of macrophage polarization are reviewed first in this paper. It is found that macrophage polarization involves several molecular mechanisms, mainly including TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, and miRNA signaling pathways. In addition, this paper also expounds the role and mechanism of macrophage polarization in various liver diseases, which aims to provide references for further research of macrophage polarization in liver diseases, contributing to the therapeutic strategy of ameliorating liver diseases by modulating macrophage polarization.
Author	Li, Yunxia Ma, Cheng Guo, Yuqin Fu, Ke Zhang, Yafang Wang, Cheng Gong, Lihong Zhou, Honglin
AuthorAffiliation	State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu , China
AuthorAffiliation_xml	– name: State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu , China
Author_xml	– sequence: 1 givenname: Cheng surname: Wang fullname: Wang, Cheng organization: State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China – sequence: 2 givenname: Cheng surname: Ma fullname: Ma, Cheng organization: State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China – sequence: 3 givenname: Lihong surname: Gong fullname: Gong, Lihong organization: State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China – sequence: 4 givenname: Yuqin surname: Guo fullname: Guo, Yuqin organization: State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China – sequence: 5 givenname: Ke surname: Fu fullname: Fu, Ke organization: State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China – sequence: 6 givenname: Yafang surname: Zhang fullname: Zhang, Yafang organization: State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China – sequence: 7 givenname: Honglin surname: Zhou fullname: Zhou, Honglin organization: State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China – sequence: 8 givenname: Yunxia surname: Li fullname: Li, Yunxia organization: State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Copyright	Copyright © 2021 Wang, Ma, Gong, Guo, Fu, Zhang, Zhou and Li. Copyright © 2021 Wang, Ma, Gong, Guo, Fu, Zhang, Zhou and Li 2021 Wang, Ma, Gong, Guo, Fu, Zhang, Zhou and Li
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Keywords	viral hepatitis alcoholic liver disease liver fibrosis liver disease macrophage polarization metabolic-associated fatty liver disease hepatocellular carcinoma acute liver injury
Language	English
License	Copyright © 2021 Wang, Ma, Gong, Guo, Fu, Zhang, Zhou and Li. 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.
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Notes	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 This article was submitted to Antigen Presenting Cell Biology, a section of the journal Frontiers in Immunology These authors have contributed equally to this work Edited by: Yan Shi, Tsinghua University, China Reviewed by: Katsunori Yoshida, Kansai Medical University, Japan; Yifang Gao, The First Affiliated Hospital of Sun Yat-sen University, China
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SubjectTerms	acute liver injury alcoholic liver disease Animals Biomarkers Cell Differentiation Cell Plasticity - genetics Cell Plasticity - immunology Diagnosis, Differential Disease Susceptibility - immunology Energy Metabolism Gene Expression Regulation Humans Immunology liver disease Liver Diseases - diagnosis Liver Diseases - etiology Liver Diseases - metabolism Liver Diseases - therapy Macrophage Activation - genetics Macrophage Activation - immunology macrophage polarization Macrophages - immunology Macrophages - metabolism Macrophages - pathology metabolic-associated fatty liver disease Organ Specificity - genetics Organ Specificity - immunology Phenotype Signal Transduction viral hepatitis
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Title	Macrophage Polarization and Its Role in Liver Disease
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