Cytoplasmic zinc promotes IL-1β production by monocytes and macrophages through mTORC1-induced glycolysis in rheumatoid arthritis

Bonah Kim; Hee Young Kim; Bo Ruem Yoon; Jina Yeo; Ji In Jung; Kyung-Sang Yu; Hyeon Chang Kim; Su-Jin Yoo; Jin Kyun Park; Seong Wook Kang; Won-Woo Lee

doi:10.1126/scisignal.abi7400

Fcγ receptor profile of monocytes and macrophages from rheumatoid arthritis patients and their response to immune complexes formed with autoantibodies to citrullinated proteins

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.142091 ◽

2011 ◽

Vol 70 (6) ◽

pp. 1052-1059 ◽

Cited By ~ 62

Author(s):

Lætitia Laurent ◽

Cyril Clavel ◽

Olivia Lemaire ◽

Florence Anquetil ◽

Martin Cornillet ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Immune Complexes ◽

Cell Types ◽

Biological Data ◽

Fcγ Receptor ◽

Necrosis Factor Alpha ◽

Monocytes And Macrophages ◽

Citrullinated Proteins ◽

Factor Alpha

ObjectiveTo analyse Fcγ receptor (FcγR) expression on monocytes and macrophages from rheumatoid arthritis (RA) patients versus healthy controls (HC), and to compare their responses to immune complexes containing RA-specific anti-citrullinated proteins auto antibodies (ACPA).MethodsMonocytes and monocyte-derived macrophages were obtained from the peripheral blood of 34 RA patients and 69 HC. FcγR expression was studied by flow cytometry. Cells were stimulated with ACPA-containing immune complexes, and tumour necrosis factor alpha (TNFα) was assayed in culture supernatants.ResultsVariations distinguished RA from HC monocytes, corresponding to a 5% and 6% decrease in the percentages of monocytes expressing FcγRI and FcγRII, respectively, and a 7% increase in the proportion of FcγRIII-positive monocytes. Although in both HC and RA patients macrophage differentiation was accompanied by a dramatic increase in the percentage of FcγRIII-expressing cells (72% vs 74.5%), the parallel decline in the proportion of FcγRI-positive cells was markedly smaller in RA (7% vs 43%). Monocytes and macrophages from patients were responsive to ACPA-containing immune complexes but TNFα production in both cell types neither differed from that observed with the corresponding cells from HC, nor correlated with FcγR expression or clinical or biological data. In RA as in HC, ACPA-containing immune complexes induced secretions of more TNFα in macrophages than in paired monocytes (ninefold). Finally, the proinflammatory potential of ACPA-containing immune complexes was confirmed in CD14-positive monocyte macrophages from the synovial fluid of four RA patients.ConclusionsACPA-containing immune complexes induce TNFα secretion by blood and synovial fluid-derived macrophages from RA patients, fitting with their probable involvement in RA pathophysiology.

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Study of Monocytes/Macrophages Stimuli as the Targets of Treating Inflammatory Bone Diseases

Current Drug Targets ◽

10.2174/1389450120666191015211737 ◽

2020 ◽

Vol 21 (4) ◽

pp. 338-343

Author(s):

Yuan Liu ◽

Yang Cao ◽

Wanli Smith ◽

Baorong He ◽

Liang Yan

Keyword(s):

Rheumatoid Arthritis ◽

Bone Diseases ◽

Cell Models ◽

Current Review ◽

Monocytes And Macrophages ◽

Orthopedic Diseases

Inflammation is the most common pathology in many orthopedic diseases, such as: rheumatoid arthritis (RA), osteoarthritis (OA) and other reasons caused osteolysis. The leading factor of inflammation was considered as the differentiation of monocyte and the polarization of macrophage. However, cytokines and different cell models could regulate this progress in some aspects. Therefore, in the current review, we summarize several cytokines and cell models, which could lead to inflammatory orthopedic diseases via regulating monocytes and macrophages. In order to extensively explore the potential therapeutic and medicine targets for inflammation-induced bone diseases.

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α-Enolase Expressed on the Surfaces of Monocytes and Macrophages Induces Robust Synovial Inflammation in Rheumatoid Arthritis

The Journal of Immunology ◽

10.4049/jimmunol.1102073 ◽

2012 ◽

Vol 189 (1) ◽

pp. 365-372 ◽

Cited By ~ 60

Author(s):

Seyeon Bae ◽

Hyemin Kim ◽

Naeun Lee ◽

Cheolhee Won ◽

Hang-Rae Kim ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Inflammation ◽

Monocytes And Macrophages

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Tuning Monocytes and Macrophages for Personalized Therapy and Diagnostic Challenge in Rheumatoid Arthritis

Cells ◽

10.3390/cells10081860 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1860

Author(s):

Leszek Roszkowski ◽

Marzena Ciechomska

Keyword(s):

Rheumatoid Arthritis ◽

Bone Erosion ◽

Cellular Heterogeneity ◽

Diagnostic Challenge ◽

Biologic Drugs ◽

Therapeutic Modalities ◽

Inflammatory Monocytes ◽

Monocytes And Macrophages ◽

Inflammatory State ◽

New Biomarkers

Monocytes/macrophages play a central role in chronic inflammatory disorders, including rheumatoid arthritis (RA). Activation of these cells results in the production of various mediators responsible for inflammation and RA pathogenesis. On the other hand, the depletion of macrophages using specific antibodies or chemical agents can prevent their synovial tissue infiltration and subsequently attenuates inflammation. Their plasticity is a major feature that helps the switch from a pro-inflammatory phenotype (M1) to an anti-inflammatory state (M2). Therefore, understanding the precise strategy targeting pro-inflammatory monocytes/macrophages should be a powerful way of inhibiting chronic inflammation and bone erosion. In this review, we demonstrate potential consequences of different epigenetic regulations on inflammatory cytokines production by monocytes. In addition, we present unique profiles of monocytes/macrophages contributing to identification of new biomarkers of disease activity or predicting treatment response in RA. We also outline novel approaches of tuning monocytes/macrophages by biologic drugs, small molecules or by other therapeutic modalities to reduce arthritis. Finally, the importance of cellular heterogeneity of monocytes/macrophages is highlighted by single-cell technologies, which leads to the design of cell-specific therapeutic protocols for personalized medicine in RA in the future.

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miR-155 overexpressing monocytes resemble HLA highISG15 + synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T cell activation

Clinical & Experimental Immunology ◽

10.1093/cei/uxab016 ◽

2021 ◽

Author(s):

Anton M Olsson ◽

Giovanni A M Povoleri ◽

Domenico Somma ◽

Michael L Ridley ◽

Tatiana Rizou ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Tissue ◽

T Cell Activation ◽

Cell Activation ◽

Adaptive Immune Response ◽

Myeloid Cells ◽

Myeloid Cell ◽

Specific Gene ◽

Monocytes And Macrophages ◽

Inhibitory Molecules

Abstract MicroRNAs (miRs) are known to regulate pro-inflammatory effector functions of myeloid cells, and miR dysregulation is implicated in rheumatoid arthritis (RA), a condition characterised by inflammation and destruction of the joints. We showed previously that miR-155 is increased in myeloid cells in RA and induces pro-inflammatory activation of monocytes and macrophages, however its role at the interface between innate and adaptive immunity was not defined. Here, RNA-sequencing revealed that overexpression of miR-155 in healthy donor monocytes conferred a specific gene profile which bears similarities to that of RA synovial fluid-derived CD14+ cells and HLA highISG15 + synovial tissue macrophages, both of which are characterised by antigen presenting pathways. In line with this, monocytes in which miR-155 was overexpressed, displayed increased expression of HLA-DR and both co-stimulatory and co-inhibitory molecules, and induced activation of polyfunctional T cells. Together, these data underpin the notion that miR-155-driven myeloid cell activation in the synovium contributes not only to inflammation but may also influence the adaptive immune response.

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