Regulatory Mechanism of M1/M2 Macrophage Polarization in the Development of Autoimmune Diseases

Abstract

Macrophages are innate immune cells in the organism and can be found in almost tissues and organs. They are highly plastic and heterogeneous cells and can participate in the immune response, thereby playing a crucial role in maintaining the immune homeostasis of the body. It is well known that undifferentiated macrophages can polarize into classically activated macrophages (M1 macrophages) and alternatively activated macrophages (M2 macrophages) under different microenvironmental conditions. The directions of macrophage polarization can be regulated by a series of factors, including interferon, lipopolysaccharide, interleukin, and noncoding RNAs. To elucidate the role of macrophages in various autoimmune diseases, we searched the literature on macrophages with the PubMed database. Search terms are as follows: macrophages, polarization, signaling pathways, noncoding RNA, inflammation, autoimmune diseases, systemic lupus erythematosus, rheumatoid arthritis, lupus nephritis, Sjogren’s syndrome, Guillain-Barré syndrome, and multiple sclerosis. In the present study, we summarize the role of macrophage polarization in common autoimmune diseases. In addition, we also summarize the features and recent advances with a particular focus on the immunotherapeutic potential of macrophage polarization in autoimmune diseases and the potentially effective therapeutic targets.

Nintedanib downregulates the profibrotic M2 phenotype in cultured monocyte-derived macrophages obtained from systemic sclerosis patients affected by interstitial lung disease

“…Current research clearly demonstrated that macrophages are characterized by a high plasticity, and they can polarize into different phenotypes depending on the microenvironment conditions and stimuli; the traditional classification identified two polarized macrophage subsets, called classically activated (M1) and alternatively activated (M2) macrophages, which represent the extremes of a broader spectrum of functional states ( 8 – 9 ). Furthermore, once macrophages adopt a particular phenotype, they can change its polarization in response to new environmental stimuli [ 10 , 11 ].…”

Administration of Liposomal-Based Pde3b Gene Therapy Protects Mice Against Collagen-Induced Rheumatoid Arthritis via Modulating Macrophage Polarization

“… 9 Compelling evidence has demonstrated that classically activated macrophages secrete high levels of proinflammatory cytokines and chemokines, leading to exacerbated symptoms and signs of RA, whereas alternatively activated macrophages restrain inflammatory responses and repair damaged tissues. 37 , 38 Indeed, reprogramming macrophages toward anti-inflammatory phenotype alleviates synovial inflammation and joint destruction in collagen-induced arthritic mice. 9 In this study, we transfected BMDMs with Pde3b siRNA, and then treated with IL-4 to determine the impact of Pde3b on macrophage polarization.…”

Characterisation of macrophage infiltration and polarisation based on integrated transcriptomic and histological analyses in Primary Sjögren’s syndrome

“…In this study, macrophages were found to be widely distributed in injured ducts and acini and co-localised with other important immune cells (including T cells and B cells) in the glandular immune microenvironment. Recent studies have shown that the abundance of M1 macrophages and expression of related inflammatory factors are high in the early stage of pSS, whereas M2 macrophages appear in the later stage of the disease and mediate chronic inflammation leading to irreversible salivary gland fibrosis (66,67). In addition, macrophages participate in CD4 + T-cell activation (66,68) and play an indispensable role in the development and maturation of B cells.…”

“…Recent studies have shown that the abundance of M1 macrophages and expression of related inflammatory factors are high in the early stage of pSS, whereas M2 macrophages appear in the later stage of the disease and mediate chronic inflammation leading to irreversible salivary gland fibrosis (66,67). In addition, macrophages participate in CD4 + T-cell activation (66,68) and play an indispensable role in the development and maturation of B cells. Deletion of macrophages results in poor Tfh cell activation (69).…”