Synovial Macrophages in Rheumatoid Arthritis: The Past, Present, and Future

Tu, Jiajie; Wang, Xinming; Gong, Xun; Hong, Wenming; Han, Dafei; Fang, Yingying; Guo, Yawei; Wei, Wei

doi:10.1155/2020/1583647

Cited by 33 publications

(25 citation statements)

References 54 publications

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“…Besides producing inflammatory cytokines and chemokines, monocytes/macrophages also play a role in adaptive immune system, which involves the pathogenesis of RA (13). In RA synovium, CD14 + cells co-locate with CD4 + T cells, indicating that monocytes/macrophages and T cells may crosstalk in vivo in an inflammatory environment (17).…”

Section: Macrophages Promote the Hyper-activation Of T Cells In Ramentioning

confidence: 99%

“…The ratio of inflammatory(M1) and antiinflammatory(M2) macrophages is impaired in RA (9). CD14 + Bone marrow (BM) monocytes/macrophages are present in the joint synovium of RA patients, and they produce co-stimulatory molecules and inflammatory cytokines, and present an active phenotype (12,13). In RA synovial fluid, the frequency of CD14 + +/bright CD16 + monocyte population increase compared to that of healthy controls (14).…”

Section: Introductionmentioning

confidence: 99%

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A Tale of Two Immune Cells in Rheumatoid Arthritis: The Crosstalk Between Macrophages and T Cells in the Synovium

Wei²,

Zhang³

et al. 2021

Front. Immunol.

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Joint inflammation of RA is closely related to infiltration of immune cells, synovium hyperplasia, and superfluous secretion of proinflammatory cytokines, which lead to cartilage degradation and bone erosion. The joint synovium of RA patients contains a variety of immune cellular types, among which monocytes/macrophages and T cells are two essential cellular components. Monocytes/macrophages can recruit and promote the differentiation of T cells into inflammatory phenotypes in RA synovium. Similarly, different subtypes of T cells can recruit monocytes/macrophages and promote osteoblast differentiation and production of inflammatory cytokines. In this review, we will discuss how T cell-monocyte/macrophage interactions promote the development of RA, which will provide new perspectives on RA pathogenesis and the development of targeted therapy.

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Section: Macrophages Promote the Hyper-activation Of T Cells In Ramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Tale of Two Immune Cells in Rheumatoid Arthritis: The Crosstalk Between Macrophages and T Cells in the Synovium

Wei²,

Zhang³

et al. 2021

Front. Immunol.

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“…Synovial tissue macrophages were previously identified by highly expressing CD68 and CD163 (50). From these populations, lining synovial macrophages were discriminated from sub-lining cells by their expression of FcgRIIIa suggesting that macrophages in the lining layer play an important role in cellular clearance (51,52).…”

Section: Role Of Tissue Resident Synovial Cells In Joint Homeostasismentioning

confidence: 99%

Critical Role of Synovial Tissue–Resident Macrophage and Fibroblast Subsets in the Persistence of Joint Inflammation

Kemble

Croft

2021

Front. Immunol.

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Rheumatoid arthritis (RA) is a chronic prototypic immune-mediated inflammatory disease which is characterized by persistent synovial inflammation, leading to progressive joint destruction. Whilst the introduction of targeted biological drugs has led to a step change in the management of RA, 30-40% of patients do not respond adequately to these treatments, regardless of the mechanism of action of the drug used (ceiling of therapeutic response). In addition, many patients who acheive clinical remission, quickly relapse following the withdrawal of treatment. These observations suggest the existence of additional pathways of disease persistence that remain to be identified and targeted therapeutically. A major barrier for the identification of therapeutic targets and successful clinical translation is the limited understanding of the cellular mechanisms that operate within the synovial microenvironment to sustain joint inflammation. Recent insights into the heterogeneity of tissue resident synovial cells, including macropahges and fibroblasts has revealed distinct subsets of these cells that differentially regulate specific aspects of inflammatory joint pathology, paving the way for targeted interventions to specifically modulate the behaviour of these cells. In this review, we will discuss the phenotypic and functional heterogeneity of tissue resident synovial cells and how this cellular diversity contributes to joint inflammation. We discuss how critical interactions between tissue resident cell types regulate the disease state by establishing critical cellular checkpoints within the synovium designed to suppress inflammation and restore joint homeostasis. We propose that failure of these cellular checkpoints leads to the emergence of imprinted pathogenic fibroblast cell states that drive the persistence of joint inflammation. Finally, we discuss therapeutic strategies that could be employed to specifically target pathogenic subsets of fibroblasts in RA.

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“…In RA, the respective functions of the distinct macrophage subsets have now been well explored, and macrophages originating from recruited monocytes appear to have overall disease-promoting functions ( 150 , 151 ). Similarly, the majority of studies on OA-affected joints have identified inflammatory, monocyte-derived macrophages as the main culprit in promoting and sustaining inflammation ( 124 , 152 ).…”

Section: Monocyte and Macrophage Functions In The Injured And Osteo-arthritic Jointmentioning

confidence: 99%

Monocytes, Macrophages, and Their Potential Niches in Synovial Joints – Therapeutic Targets in Post-Traumatic Osteoarthritis?

et al. 2021

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Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: “a macrophage niche”. These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.

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Synovial Macrophages in Rheumatoid Arthritis: The Past, Present, and Future

Cited by 33 publications

References 54 publications

A Tale of Two Immune Cells in Rheumatoid Arthritis: The Crosstalk Between Macrophages and T Cells in the Synovium

A Tale of Two Immune Cells in Rheumatoid Arthritis: The Crosstalk Between Macrophages and T Cells in the Synovium

Critical Role of Synovial Tissue–Resident Macrophage and Fibroblast Subsets in the Persistence of Joint Inflammation

Monocytes, Macrophages, and Their Potential Niches in Synovial Joints – Therapeutic Targets in Post-Traumatic Osteoarthritis?

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