Artikel
Dopamine is involved in B cell function in female rheumatoid arthritis patients
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Autoren
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Silvia Capellino
- IfADo – Leibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Neuroimmunology research group, Dortmund
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Karolin Wieber
- IfADo – Leibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Neuroimmunology research group, Dortmund
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Leonie Fleige
- IfADo – Leibniz Research Centre for Working Environment and Human Factors, Department of Immunology, Neuroimmunology research group, Dortmund
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Styliani Tsiami
- Rheumazentrum Ruhrgebiet Herne, Ruhr University Bochum, Bochum
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Jörg Reinders
- IfADo – Leibniz Research Centre for Working Environment and Human Factors, Department of Toxicology, Analytical Chemistry, Dortmund
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Jürgen Braun
- Rheumazentrum Ruhrgebiet Herne, Ruhr University Bochum, Bochum
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Xenofon Baraliakos
- Rheumazentrum Ruhrgebiet Herne, Ruhr University Bochum, Bochum
| Veröffentlicht: | 14. September 2021 |
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Gliederung
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Background: Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and consequently joint destruction. However, RA is not simply a disease of the joints but a systemic inflammation. Within the immune cells involved, B cells play critical roles in RA pathogenesis, and their depletion is an effective therapeutic strategy. However, total B cell depletion leads to immune depression. Therefore, a novel therapy targeting only proinflammatory B cells would be preferable. Growing evidence suggests an involvement of dopamine in RA. Based on this knowledge, we investigated the role of dopamine on B cell activation in RA.
Methods: Peripheral blood mononuclear cells (PBMCs) from healthy controls (HC, n=35) and RA patients (n=30) were investigated for expression of D1-D5 dopamine receptors (DR) by flow cytometry (FACS). Additionally, D1-like DR were stimulated with selective agonists in vitro to assess effects on immune cell activation, proliferation, and differentiation. FACS analysis was performed for quantifying cell marker expression and cell proliferation, whereas ELISAs were conducted to measure cytokine secretion and dopamine levels. The study was approved by the ethical committee and patients gave written consent.
Results: All five DR were expressed in PBMCs from HC and RA patients. Dopamine was detectable only in RA PBMCs. A significantly higher expression of D1DR was identified in peripheral B cells of RA female patients compared to female HC. D1DR expression in B cells of female RA patients positively correlated with disease duration and increased during maturation. In T cell-independent B cell stimulation, D1-like receptor stimulation upregulated CCL-3 release specifically in female RA. Furthermore, in PBMCs from female RA patients, D1-like receptor stimulation led to higher IL-8 secretion compared to HC, which is relevant for bone destruction.
Conclusion: Increased levels of D1DR and dopamine are present in peripheral B cells of RA female patients and may play pivotal roles by enhancing maturation and function of pathogenic B cells. These findings highlight the blockade of D1DR on peripheral B cells as potential new therapeutic target in RA. Further studies are necessary to clarify the exact mechanisms of action of dopamine on B cells as well as possible effects also in men.
Disclosures: Nothing to disclose.
