Macrophage Polarization and Its Role in Liver Disease

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.

LncRNA NEAT1 Potentiates SREBP2 Activity to Promote Inflammatory Macrophage Activation and Limit Hantaan Virus Propagation

“…The production of another nine chemokines, including CCL1, CCL7, CCL17 and others, was decreased once N-SREBP was overexpressed ( Figure 4H ). However, the production of IFNγ, IL-4 and IL-10, which are canonical cytokines that stimulate M1 or M2 polarization ( Wang et al, 2021 ), as well as 10 other kinds of cytokines, showed no significant conversion between the eGFP- and N-SREBP-overexpressing groups ( Figure 4I ). These data clarified that SREBP could promote the secretion of various inflammatory cytokines in macrophages to fight HTNV infection.…”

“…The classical inflammatory activation pattern of macrophages (M1 polarization) or monocytes (M1-like monocytes), which is stimulated by host Th1-type cytokines (such as interferon-γ/IFNγ and tumor necrosis factor-α/TNFα) or pathogen-associated molecular patterns (PAMPs) via JAK/STAT, NF-κB or pattern-recognition receptor (PRR)-mediated signaling, maintains the potential ability of the immune system to restrict viral infection and promote virus clearance by initiating a robust interferon-centered inflammation response, the dysregulation of which triggers a cytokine storm and aggravates host immunopathological injury ( McNab et al, 2015 ; Merad and Martin, 2020 ; McGonagle et al, 2021 ). Alternatively, macrophages can be M2-polarized by Th2-type cytokines (such as IL-4 and IL-10), which promote the resolution of inflammatory responses and assist in tissue repair ( Wang et al, 2021 ). It has been reported that hantavirus (strain no.…”

Spatial maps of hepatocellular carcinoma transcriptomes reveal spatial expression patterns in tumor immune microenvironment

“…Clinical relevance analysis also indicated that high expression of CCL15 or the M2-like macrophage marker CD163 predict a poor prognosis of HCC and the combined predictive value of CCL15 and CD163 in the prognosis is superior to that using either marker alone. Currently, macrophage polarization involves a variety of molecular mechanisms, including TLR4/NF-κB, JAK/STATS, TGF-β/SMADS, PPARγ, NOTCH and microRNA signaling pathways 56 , however, the detailed mechanism driving M2-like macrophages by CCL15 will be our future work.…”

Heterogeneity and Function of Kupffer Cells in Liver Injury

“…For example, KCs are activated into M1 phenotype by lipopolysaccharide (LPS), IFN-gamma or M-CSF, characterizing by highly expressing pro-inflammatory genes IL1B, TNFα and iNOS ( 36 ). While IL4 or GM-CSF may polarize KCs into M2 type that highly express ARG1, IL10 and MRC1 ( 27 , 28 ). However, later studies found that M1-M2 dichotomy is insufficient to classify KCs, especially in liver injury ( 37 , 38 ).…”