Open this publication in new window or tab >>Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Unité Propre de Recherche (UPR) Centre National de la Recherche Scientifique (CNRS) 4301Centre de Biophysique Moléculaire (CBM), Département NanoMédicaments et NanoSondes (NMNS), Tours, France; Université de Tours, Unité de Formation et de Recherche (UFR) de Médecine, Tours Cedex 1, France; Centre Hospitalier Universitaire (CHU) de Tours, Service de Rhumatologie, Tours Cedex 9, France.
Lymphocytes B, Autoimmunité et Immunothérapies (LBAI) Unité Mixte de Recherche (UMR) 1227, Institut National de la Santé et de la Recherche Médicale (INSERM), Brest, France; Université de Bretagne Occidentale, Faculté de Médecine et Sciences de la Santé, Brest Cedex 3, France; Centre Hospitalier Régional Universitaire (CHRU) de Brest, Service de Rhumatologie, Brest, France.
Lymphocytes B, Autoimmunité et Immunothérapies (LBAI) Unité Mixte de Recherche (UMR) 1227, Institut National de la Santé et de la Recherche Médicale (INSERM), Brest, France; Université de Bretagne Occidentale, Faculté de Médecine et Sciences de la Santé, Brest Cedex 3, France; Centre Hospitalier Régional Universitaire (CHRU) de Brest, Service de Rhumatologie, Brest, France.
Lymphocytes B, Autoimmunité et Immunothérapies (LBAI) Unité Mixte de Recherche (UMR) 1227, Institut National de la Santé et de la Recherche Médicale (INSERM), Brest, France; Université de Bretagne Occidentale, Faculté de Médecine et Sciences de la Santé, Brest Cedex 3, France; Centre Hospitalier Régional Universitaire (CHRU) de Brest, Service de Rhumatologie, Brest, France.
Lymphocytes B, Autoimmunité et Immunothérapies (LBAI) Unité Mixte de Recherche (UMR) 1227, Institut National de la Santé et de la Recherche Médicale (INSERM), Brest, France; Université de Bretagne Occidentale, Faculté de Médecine et Sciences de la Santé, Brest Cedex 3, France; Centre Hospitalier Régional Universitaire (CHRU) de Brest, Service de Rhumatologie, Brest, France.
Lymphocytes B, Autoimmunité et Immunothérapies (LBAI) Unité Mixte de Recherche (UMR) 1227, Institut National de la Santé et de la Recherche Médicale (INSERM), Brest, France; Centre Hospitalier Régional Universitaire (CHRU) de Brest, Service de Rhumatologie, Brest, France.
Department of Laboratory Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Department of Radiology, Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Rheumatology, Southend University Hospital National Health Service (NHS) Foundation Trust, Westcliff-on-Sea, UK.
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Show others...
2025 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060Article in journal (Refereed) Epub ahead of print
Abstract [en]
OBJECTIVES: Insight into the immunopathology of polymyalgia rheumatica (PMR) is scarce and mainly derived from peripheral blood studies. The limited data available point towards macrophages as potential key players in PMR. This study aimed to identify the factors driving proinflammatory macrophage development and their functions in the immunopathology of PMR.
METHODS: Monocyte phenotypes were investigated by flow cytometry in peripheral blood (PMR, n = 22; healthy controls, n = 20) and paired subacromial-subdeltoid (SASD) bursal fluid (PMR, n = 9). Macrophages in SASD bursa were characterised by immunohistochemistry and immunofluorescence (PMR, n = 12; controls undergoing shoulder replacement surgery, n = 10). The functions of cytokines expressed in PMR-affected tissue were examined using macrophage differentiation cultures (PMR, n = 7; healthy controls, n = 7).
RESULTS: Monocytes (CD14highCD16- and CD14highCD16+) were increased in blood of PMR patients and activated in bursal fluid. Macrophages dominated immune infiltrates in PMR-affected tissue, expressing various proinflammatory cytokines. While interleukin (IL)-6 and interferon-gamma (IFN-γ) expression was abundant in both PMR and control tissue, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) were significantly increased in PMR tissue. Macrophages in PMR-affected tissue showed an elevated CD206/folate receptor β ratio, reflecting a GM-CSF skewed signature. A combination of GM-CSF/M-CSF/IFN-γ significantly boosted IL-6 production in vitro, while limited IL-6 production was observed without GM-CSF.
CONCLUSIONS: The monocyte compartment is expanded and activated in PMR. Macrophages in PMR-affected tissue produce abundant proinflammatory cytokines such as IL-6. A network of locally expressed cytokines, including GM-CSF, M-CSF, and IFN-γ, may drive the proinflammatory functions of these macrophages. Overall, macrophages may constitute key therapeutic targets for PMR.
Place, publisher, year, edition, pages
Highwire Press, 2025
National Category
Immunology in the medical area Cell and Molecular Biology
Identifiers
urn:nbn:se:oru:diva-119175 (URN)10.1016/j.ard.2025.01.004 (DOI)39915203 (PubMedID)
Note
Funding Agencies:
The study was supported by a research grant from FOREUM Foundation for Research in Rheumatology (Career Research Grant; KSMvdG). The study was also funded by the Dutch Society for Rheumatology (Rheumatology Grant; KSMvdG), the University of Groningen (AZ), the State Scholarship Fund China (AZ), and the Mandema Stipend (KSMvdG).
2025-02-072025-02-072025-02-07Bibliographically approved