Cytokine producing B-cells and their capability to polarize macrophages in giant cell arteritis.

Autor: Graver JC; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Jiemy WF; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Altulea DHA; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., van Sleen Y; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Xu S; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., van der Geest KSM; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Verstappen GMPJ; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Heeringa P; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Abdulahad WH; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Brouwer E; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Boots AMH; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Sandovici M; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. Electronic address: m.sandovici01@umcg.nl.
Jazyk: angličtina
Zdroj: Journal of autoimmunity [J Autoimmun] 2023 Nov; Vol. 140, pp. 103111. Date of Electronic Publication: 2023 Sep 11.
DOI: 10.1016/j.jaut.2023.103111
Abstrakt: Objective: The lack of disease-specific autoantibodies in giant cell arteritis (GCA) suggests an alternative role for B-cells readily detected in the inflamed arteries. Here we study the cytokine profile of tissue infiltrated and peripheral blood B-cells of patients with GCA. Moreover, we investigate the macrophage skewing capability of B-cell-derived cytokines.
Methods: The presence of various cytokines in B-cell areas in temporal artery (n = 11) and aorta (n = 10) was identified by immunohistochemistry. PBMCs of patients with GCA (n = 11) and polymyalgia rheumatica (n = 10), and 14 age- and sex-matched healthy controls (HC) were stimulated, followed by flow cytometry for cytokine expression in B-cells. The skewing potential of B-cell-derived cytokines (n = 6 for GCA and HC) on macrophages was studied in vitro.
Results: The presence of IL-6, GM-CSF, TNFα, IFNγ, LTβ and IL-10 was documented in B-cells and B-cell rich areas of GCA arteries. In vitro, B-cell-derived cytokines (from both GCA and HC) skewed macrophages towards a pro-inflammatory phenotype with enhanced expression of IL-6, IL-1β, TNFα, IL-23, YKL-40 and MMP-9. In vitro stimulated peripheral blood B-cells from treatment-naïve GCA patients showed an enhanced frequency of IL-6+ and TNFα+IL-6+ B-cells compared to HCs. This difference was no longer detected in treatment-induced remission. Erythrocyte sedimentation rate positively correlated with IL-6+TNFα+ B-cells.
Conclusion: B-cells are capable of producing cytokines and steering macrophages towards a pro-inflammatory phenotype. Although the capacity of B-cells in skewing macrophages is not GCA specific, these data support a cytokine-mediated role for B-cells in GCA and provide grounds for B-cell targeted therapy in GCA.
Competing Interests: Declaration of competing interest KSMvdG reports personal fees from Roche, outside the submitted work. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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