The Role of M1/M2 Macrophage Polarization in Rheumatoid Arthritis Synovitis

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: May 19, 2022

Innate and adaptive immunity represent a harmonic counterbalanced system involved in the induction, progression, possibly resolution of inflammatory reaction that characterize autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis (RA). Although immunopathophysiological mechanisms ARDs are not fully clarified, they often associated with an inappropriate macrophage/T-cell interaction, where classical (M1) or alternative (M2) macrophage activation may influence occurrence T-helper (Th)1 Th2 responses. In RA patients, M1/Th1 occurs environment dominated by Toll-like receptor (TLR) interferon (IFN) signaling, it promotes massive production pro-inflammatory cytokines [i.e., tumor necrosis factor-α (TNFα), interleukin (IL)-1, IL-12, IL-18, IFNγ], chemotactic factors, matrix metalloproteinases resulting osteoclastogenesis, erosion, progressive joint destruction. On other hand, M2/Th2 response determines release growth factors IL-4, IL-10, IL-13, transforming factor (TGF)-β] anti-inflammatory process leading to clinical remission RA. Several subtypes macrophages have been described. Five polarization states from M1 M2 confirmed vitro studies analyzing morphological characteristics, gene expression phenotype markers (CD80, CD86, TLR2, TLR4, CD206, CD204, CD163, MerTK), functional aspect, reactive oxygen species (ROS). An imbalance induce pathological consequences contribute several diseases, such as asthma osteoclastogenesis patients. addition, dynamic includes presence intermediate polarity stages distinguished specific surface production/release distinct molecules (i.e., nitric oxide, cytokines), which their state. This suggests "continuum" playing important role during inflammation its resolution. review discusses importance delicate M1/M2 different phases together identification pathways, cytokines, chemokines involved, outcomes The analysis these aspects could shed light on abnormal activation, novel therapeutical approaches restore balance.

Language: Английский

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Macrophages: The Good, the Bad, and the Gluttony

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 12, 2021

Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation. In this review, we will compile interpret recent findings on plasticity macrophages how these contribute to development non-infectious inflammatory diseases, with a particular focus allergic autoimmune disorders. The inflammation then be examined, emphasizing ability clear apoptotic immune cells. Rheumatoid arthritis (RA) is chronic autoimmune-driven spectrum diseases where persistent results synovial hyperplasia excessive cell accumulation, leading remodeling reduced function affected joints. central pathophysiology RA, driving episodic cycles tissue destruction. RA patients have increased numbers active M1 polarized pro-inflammatory few or inactive M2 type This imbalance macrophage homeostasis main contributor mediators resulting continual activation stromal populations accelerated remodeling. Modulation phenotype remains key therapeutic goal for treatment disease. Intriguingly, intervention glucocorticoids other DMARDs promotes re-polarization an anti-inflammatory phenotype; reprogramming dependent metabolic changes promote phenotypic switching. Allergic asthma associated Th2-polarised airway inflammation, structural large airways, hyperresponsiveness. Macrophage polarization has profound impact pathogenesis, as response allergen exposure regulated by intricate interplay between local factors including cytokines, chemokines danger signals from neighboring Th2-polarized environment characteristic asthma, high levels IL-4 produced locally infiltrating innate lymphoid helper T acquisition alternatively activated M2a macrophages, myriad effects structure. Targeting regulators currently being pursued diseases. re-balancing responses towards pro-resolution thus success response. It long been established apoptosis supports monocyte recruitment sites facilitating subsequent corpse clearance. drives mediates switch polarity macrophages. However, role cell-derived extracellular vesicles (ACdEV) control received remarkably little attention. ACdEV powerful intercellular communication, carrying wealth lipid protein may modulate phenotype, cargo immune-modulating enzymes. such interactions result repair disease different contexts. discuss origin, characterization, activity underlying mechanisms via clearance, order provide new insights into strategies could exploit capabilities agile responsive

Language: Английский

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Synovial tissue macrophages in joint homeostasis, rheumatoid arthritis and disease remission

Nature Reviews Rheumatology, Journal Year: 2022, Volume and Issue: 18(7), P. 384 - 397

Published: June 7, 2022

Language: Английский

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Anti-rheumatoid drugs advancements: New insights into the molecular treatment of rheumatoid arthritis

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 151, P. 113126 - 113126

Published: May 26, 2022

Rheumatoid arthritis (RA) is one of more than 100 types arthritis. This chronic autoimmune disorder affects the lining synovial joints in about 0.5% people and may induce severe deformity disability. RA impacts health life from all sexes ages with prevalence elderly women people. Significant improvement has been noted last two decades revealing mechanisms development RA, early diagnosis new treatment options. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying antirheumatic (DMARDs) remain most known treatments used against RA. However, not patients respond well to these therefore, solutions are immense need improve disease outcomes. In present review, we discuss highlight recent findings concerning different classes therapies including conventional modern drug therapies, as emerging options phyto-cannabinoid cell- RNA-based therapies. A better understanding their pathways might help find a specific target inflammation, cartilage damage, reduce side effects

Language: Английский

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Macrophage: Key player in the pathogenesis of autoimmune diseases

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 14, 2023

The macrophage is an essential part of the innate immune system and also serves as bridge between immunity adaptive response. As initiator executor response, plays important role in various physiological processes such tolerance, fibrosis, inflammatory angiogenesis phagocytosis apoptotic cells. Consequently, dysfunction a vital cause occurrence development autoimmune diseases. In this review, we mainly discuss functions macrophages diseases, especially systemic lupus erythematosus (SLE), rheumatic arthritis (RA), sclerosis (SSc) type 1 diabetes (T1D), providing references for treatment prevention

Language: Английский

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Sinomenine ameliorates rheumatoid arthritis by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation

Science Bulletin, Journal Year: 2023, Volume and Issue: 68(14), P. 1540 - 1555

Published: June 28, 2023

Gut microbiota dysbiosis is associated with the development of rheumatoid arthritis (RA). Sinomenine (SIN) an effective immunosuppressive and anti-inflammatory drug used for treating RA, but how SIN regulates gut to alleviate RA remains underexplored. To identify critical microbial species metabolites RA-protective effects SIN, microbiota-dependent anti-RA were assessed by 16S rRNA gene sequencing, antibiotic treatment, fecal transplantation. Metabolomics analysis, transcriptional targeted bacteria/metabolites gavage conducted explore reduce severity RA. could restore intestinal balance mainly modulating abundance Lactobacillus, significantly relieve collagen-induced (CIA) symptoms in a manner. elevated tryptophan indole-3-acrylic acid (IA), indole-3-propionic (IPA), indole-3-acetic (IAA). Tryptophan supplementation activate aryl hydrocarbon receptor (AhR) regulate Th17/Treg CIA rats. Intriguingly, relieved involving enrichment two beneficial anti-CIA Lactobacillus species, L. paracasei casei mono-colonization. The promising therapeutic function was mostly attributed activation AhR explicitly targeting metabolites. bacterium may be CIA.

Language: Английский

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

Mediators of Inflammation, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 20

Published: June 8, 2023

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

Language: Английский

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Rheumatoid arthritis: pathogenesis and therapeutic advances

MedComm, Journal Year: 2024, Volume and Issue: 5(3)

Published: March 1, 2024

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the unresolved synovial inflammation for tissues‐destructive consequence, which remains one of significant causes disability and labor loss, affecting about 0.2–1% global population. Although treatments with disease‐modifying antirheumatic drugs (DMARDs) are effective to control decrease bone destruction, overall remission rates RA still stay at low level. Therefore, uncovering pathogenesis expediting clinical transformation imminently in need. Here, we summarize immunological basis, inflammatory pathways, genetic epigenetic alterations, metabolic disorders RA, highlights on abnormality immune cells atlas, epigenetics, immunometabolism. Besides an overview first‐line medications including conventional DMARDs, biologics, small molecule agents, discuss depth promising targeted therapies under or preclinical trials, especially regulators. Additionally, prospects precision medicine based biopsy RNA‐sequencing cell mesenchymal stem chimeric antigen receptor T‐cell also looked forward. The advancements innovations accelerates progress treatments.

Language: Английский

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Mesenchymal stem cell exosomal tsRNA-21109 alleviate systemic lupus erythematosus by inhibiting macrophage M1 polarization

Molecular Immunology, Journal Year: 2021, Volume and Issue: 139, P. 106 - 114

Published: Aug. 28, 2021

Language: Английский

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A Smart Nanoreactor Based on an O₂-Economized Dual Energy Inhibition Strategy Armed with Dual Multi-stimuli-Responsive “Doorkeepers” for Enhanced CDT/PTT of Rheumatoid Arthritis

ACS Nano, Journal Year: 2022, Volume and Issue: 16(10), P. 17062 - 17079

Published: Sept. 26, 2022

Activated fibroblast-like synovial (FLS) cells are regarded as an important target for rheumatoid arthritis (RA) treatment via starvation therapy mediated by glucose oxidase (GOx). However, the hypoxic RA-FLS environment greatly reduces oxidation process of and leads to a poor therapeutic effect GOx-based therapy. In this work, we designed hollow mesoporous copper sulfide nanoparticles (CuS NPs)-based smart GOx/atovaquone (ATO) codelivery system (named V-HAGC) targeting realize O2-economized dual energy inhibition strategy solve limitation V-HAGC armed with multi-stimuli-responsive "doorkeepers" can guard drugs intelligently. Once under stimulation photothermal acidic conditions at targeted area, intelligent responsive "doors" would orderly open controllable release drugs. Besides, efficacy be much improved additional chemodynamic (CDT) (PTT) stimulated CuS NPs. Meanwhile, upregulated H2O2 acid levels promote Fenton-like reaction NPs inhibition, which could enhance PTT CDT well. vitro in vivo evaluations revealed combination RA. general, based on combined enhanced has potential alternative methodology

Language: Английский

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