Research progress in the role of M1/M2 polarization of macrophages in different liver diseases

doi:10.3969/j.issn.1674-8115.2024.04.012

Abstract

Abstract:

Macrophages have strong plasticity and heterogeneity, and can undergo functional transformation in response to different signal stimuli, such as classical activation of M1 type (M1 type polarization) and selective activation of M2 type (M2 type polarization). The pathways of macrophage M1/M2 polarization are quite extensive, involving nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, interleukin-4 (IL-4)/signal transduction and activator of transcription 6 (STAT6) signaling pathway, Notch signaling pathway, Wnt/β-catenin signaling pathway, etc. At the same time, M1/M2 polarization of macrophages is also regulated by exosomes, metabolites, non-coding RNA, electrical stimulation, probiotics, etc., and its imbalance is closely related to the occurrence and development of different types of liver disease. In this paper, the mechanism of its polarization was reviewed, and it was found that M1 polarization of macrophages played a promoting role in the process of liver tissue injury, inflammation and fibrosis, while M2 polarization of macrophages played the opposite role. Among them, hepatocellular carcinoma, as the advanced stage of chronic liver disease, was characterized by increased M2 polarization and impaired M1 polarization of macrophages. Therefore, this paper pays attention to the role of M1/M2 polarization of macrophages in different types of liver diseases, in order to better establish the targeted therapy of macrophage subsets.

Key words: macrophage polarization, M1 macrophage, M2 macrophage, liver disease

CLC Number:

R575

NIU Yuanyuan, WANG Longde, XU Wenjuan, LI Zhengju, ZHANG Ruiting, WU Yuqian. Research progress in the role of M1/M2 polarization of macrophages in different liver diseases[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(4): 509-517.

Figures/Tables 2

TrendMD

References 60

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Macrophage polarization type	Inducer	Cytokine secretion	Biomarker	Signaling pathways affecting polarization	Functional characteristics
M1 macrophage	LPS, IFN-γ	IL-6, IL-12, IL-1β, TNF-α, NO, GFAP, iNOS	CD80, CD86, CD16/32	NF-κB, MAPK, Wnt/ β-catenin, Notch	Antigen-presenting, mediating Th1 and Th17 immune responses, proinflammatory, anti-tumor, eliminating pathogens
M2a macrophage	IL-4, IL-13	Arg-1, CCL17, IL-10, CCL22	CD206, CD103	IL-4/STAT6, MAPK, JNK-1/STAT6	Anti-inflammatory, mediating Th2 type immune response, tissue repair, allergy, fibrotic immune regulation
M2b macrophage	IL-33, LPS	IL-10, TNF-α, IL-6, TGF-β, VEGF	CD206, MHCⅡ	TLR4, PI3K
M2c macrophage	TGF-β, IL-10	Arg-1, TGF-β, CXCL13	CD163, CD206	JAK/STAT3, NF-κB, TGF-β/Smads	Phagocytosis, immunosuppression
M2d macrophage	TLR agonist	IL-10, VEGF, IL-12^low, TNF-α^low	CD206	TLR4, NF-κB	Organizational restructuring, angiogenesis

Macrophage polarization type	Inducer	Cytokine secretion	Biomarker	Signaling pathways affecting polarization	Functional characteristics
M1 macrophage	LPS, IFN-γ	IL-6, IL-12, IL-1β, TNF-α, NO, GFAP, iNOS	CD80, CD86, CD16/32	NF-κB, MAPK, Wnt/ β-catenin, Notch	Antigen-presenting, mediating Th1 and Th17 immune responses, proinflammatory, anti-tumor, eliminating pathogens
M2a macrophage	IL-4, IL-13	Arg-1, CCL17, IL-10, CCL22	CD206, CD103	IL-4/STAT6, MAPK, JNK-1/STAT6	Anti-inflammatory, mediating Th2 type immune response, tissue repair, allergy, fibrotic immune regulation
M2b macrophage	IL-33, LPS	IL-10, TNF-α, IL-6, TGF-β, VEGF	CD206, MHCⅡ	TLR4, PI3K
M2c macrophage	TGF-β, IL-10	Arg-1, TGF-β, CXCL13	CD163, CD206	JAK/STAT3, NF-κB, TGF-β/Smads	Phagocytosis, immunosuppression
M2d macrophage	TLR agonist	IL-10, VEGF, IL-12^low, TNF-α^low	CD206	TLR4, NF-κB	Organizational restructuring, angiogenesis

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