Functional Phenotype of Synovial Monocytes Modulating Inflammatory T-Cell Responses in Rheumatoid Arthritis (RA)

Yoon, Bo Ruem; Yoo, Su Jin; Choi, Yujung; Chung, Yeon Ho; Kim, Jin Hyun; Yoo, In Seol; Kang, Seong Wook; Lee, Won Woo

doi:10.1371/journal.pone.0109775

Cited by 85 publications

(92 citation statements)

References 35 publications

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“…We previously reported that synovial monocytes possess the unique capability to promote Th1 and Th17 responses of peripheral CD4 T cells (17). Although the higher expression of surface B7-H3 was described as one of major features of synovial monocytes in the studies, we also showed the enhanced expressions of HLA-DR and CD80, which delivers "signal 1" and "signal 2" to T cells, respectively.…”

Section: Discussionmentioning

confidence: 60%

“…1, A and B) (17). To confirm our microarray data in a secondary cohort, CD14 ϩ monocytes were purified from PBMCs and SFMCs, which were prepared simultaneously from the same RA patients, and B7-H3 expression was analyzed using RT-PCR and flow cytometry.…”

Section: B7-h3 Expression Is Markedly Elevated On Synovialmentioning

confidence: 94%

“…Unlike CD80 and CD86, human B7-H3 is broadly expressed at low levels in multiple organs and markedly overexpressed on several cancers (15,16). In immune cells, B7-H3 expression is induced in human monocytes and dendritic cells by inflammatory cytokines and augmented by synovial monocytes of RA patients (11,17), indicating potential immunoregulatory function at sites of inflammation (7).…”

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confidence: 99%

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Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocytes in Rheumatoid Arthritis

Yoon¹,

Chung

Yoo

et al. 2016

Journal of Biological Chemistry

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B7-H3, a newly identified B7 family member, has functional duality as a co-stimulator and co-inhibitor that fine-tunes T cell-mediated immune responses. Given that B7-H3 expression on human monocytes and dendritic cells is enhanced by inflammatory cytokines, its potential inmmunoregulatory role at sites of inflammation has been suggested. Further, monocytes play crucial roles in the pathophysiology of various inflammatory disorders including autoimmune diseases; however, the immunological role of B7-H3 in rheumatoid arthritis (RA) has not been defined. Thus, we aimed to investigate the possible roles of monocyte B7-H3 in the pathogenesis of RA. Synovial monocytes, but not peripheral monocytes, in RA patients predominantly express surface B7-H3. The 4Ig isoform of B7-H3 is exclusively induced on the cell surface, whereas the 2Ig B7-H3 isoform is constitutively expressed in the intracytoplasmic region of both peripheral and synovial monocytes. B7-H3 knockdown experiments reveal that surface B7-H3 has an inhibitory effect on IFN-␥ production in CD4 memory cells. Moreover, surface B7-H3 expression on synovial monocytes inversely correlates with RA clinical parameters. Our findings demonstrate that activation-induced B7-H3 expression on synovial monocytes has the potential to inhibit Th1-mediated immune responses and immunomodulatory roles affecting RA pathogenesis.

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Section: Discussionmentioning

confidence: 60%

Section: B7-h3 Expression Is Markedly Elevated On Synovialmentioning

confidence: 94%

mentioning

confidence: 99%

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Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocytes in Rheumatoid Arthritis

Yoon¹,

Chung

Yoo

et al. 2016

Journal of Biological Chemistry

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“…In summary, alterations in the composition of the mobile CSF monocyte pool may reflect a shift of CD16 + monocytes from the periphery to sites of inflammation. Such a compartmentalization, which is typical for MS, may account for the difference in monocyte subgroup distributions in other autoimmune diseases (7)(8)(9)(10)(11)(12)(13)(14)(15). CD16 + non-classical so-called patrolling monocytes exert important functions in the peripheral immune compartment.…”

Section: Discussionmentioning

confidence: 99%

“…In these studies, it was demonstrated that the expansion of CD16 + monocytes is driven by the intermediate monocyte subset (9)(10)(11) and that these CD16 + monocytes actively shape T cell responses by favoring Th17 differentiation (9). Accordingly, it has been suggested that CD16 + monocytes play a pivotal role in the pathophysiology of autoimmune diseases.…”

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confidence: 99%

Pivotal Role for CD16+ Monocytes in Immune Surveillance of the Central Nervous System

Waschbisch

Schröder

Schraudner

et al. 2016

The Journal of Immunology

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Monocytes represent a heterogeneous population of primary immune effector cells. At least three different subsets can be distinguished based on expression of the low-affinity FcγRIII: CD14++CD16− classical monocytes, CD14++CD16+ intermediate monocytes, and CD14+CD16++ non-classical monocytes. Whereas CD16− classical monocytes are considered key players in multiple sclerosis (MS), little is known on CD16+ monocytes and how they contribute to the disease. In this study, we examined the frequency and phenotype of monocyte subpopulations in peripheral blood, cerebrospinal fluid (CSF), and brain biopsy material derived from MS patients and controls. Furthermore, we addressed a possible monocyte dysfunction in MS and analyzed migratory properties of monocyte subsets using human brain microvascular endothelial cells. Our ex vivo studies demonstrated that CD16+ monocyte subpopulations are functional but numerically reduced in the peripheral blood of MS patients. CD16+ monocytes with an intermediate-like phenotype were found to be enriched in CSF and dominated the CSF monocyte population under noninflammatory conditions. In contrast, an inversed CD16+ to CD16− CSF monocyte ratio was observed in MS patients with relapsing-remitting disease. Newly infiltrating, hematogenous CD16+ monocytes were detected in a perivascular location within active MS lesions, and CD16+ monocytes facilitated CD4+ T cell trafficking in a blood–brain barrier model. Our findings support an important role of CD16+ monocytes in the steady-state immune surveillance of the CNS and suggest that CD16+ monocytes shift to sites of inflammation and contribute to the breakdown of the blood–brain barrier in CNS autoimmune diseases.

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Circulating Baseline CXCR3⁺Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis

Scheffler,

Drevinge,

Lindholm

et al. 2024

ACR Open Rheumatology

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ObjectiveThe high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell–derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease‐modifying antirheumatic drugs (bDMARDs) in RA.MethodsThirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C‐reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4+ T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high‐resolution peripheral quantitative computed tomography (HR‐pQCT).ResultsHR‐pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3+Th2 cells (r = −0.38, P = 0.04) and CXCR3+Th17 cells (r = −0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing.ConclusionMTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA.

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Functional Phenotype of Synovial Monocytes Modulating Inflammatory T-Cell Responses in Rheumatoid Arthritis (RA)

Cited by 85 publications

References 35 publications

Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocytes in Rheumatoid Arthritis

Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocytes in Rheumatoid Arthritis

Pivotal Role for CD16+ Monocytes in Immune Surveillance of the Central Nervous System

Circulating Baseline CXCR3⁺Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis

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Functional Phenotype of Synovial Monocytes Modulating Inflammatory T-Cell Responses in Rheumatoid Arthritis (RA)

Cited by 85 publications

References 35 publications

Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocytes in Rheumatoid Arthritis

Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocytes in Rheumatoid Arthritis

Pivotal Role for CD16+ Monocytes in Immune Surveillance of the Central Nervous System

Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis

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Circulating Baseline CXCR3⁺Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis