Artikel
Targeted modulation of neurotransmitter receptors on specific leukocyte subpopulations: a new therapeutic approach for inflammatory rheumatic diseases
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Autoren
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Karolin Wieber
- IfADo – Leibniz Research Centre for Working Environment and Human Factors, Neuroimmunology, Dortmund
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Xenofon Baraliakos
- Rheumazentrum Ruhrgebiet, Herne
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Jürgen Braun
- Rheumazentrum Ruhrgebiet, Herne
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Silvia Capellino
- IfADo – Leibniz Research Centre for Working Environment and Human Factors, Neuroimmunology, Dortmund
| Veröffentlicht: | 5. Februar 2019 |
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Gliederung
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Background: Rheumatic diseases may cause pain and disability. Current treatment strategies are only partly successful and their side effects are rather common. Therefore, new treatment options able to differentially control only the immune pathomechanisms would be preferable.
Earlier findings emphasized a role for dopamine (DA) in the pathogenesis of rheumatoid arthritis (RA). Moreover, the DA-synthesizing enzyme tyrosine hydroxylase (TH) and dopaminergic receptors (DR) are expressed on immune cells. Our aim was to investigate alterations of the dopaminergic pathway in immune cells in different inflammatory rheumatic diseases.
Methods: The expression of TH and DRs (DRD1-5) was examined via flow cytometry in peripheral blood mononuclear cells (PBMC) of patients diagnosed with RA (n=6), psoriasis arthritis (PsA, n=4), spondylitis ankylosans (SpA, n=9) and of healthy controls (HC, n=8). Disease activity and duration was heterogeneous in all patient cohorts. In vitro experiments with DR-agonists were performed to determine immune-modulatory effects of DR-stimulation.
Results: All investigated PBMC subpopulations expressed TH and DRs, with NK cells and monocytes showing highest expression levels in all cohorts. TH expression was lower in T and NKT cells of PsA and SpA patients compared to HC. The frequency of B cells positive for DRD1 and DRD3 tended to be higher in RA and SpA patients. DRD5 expression was increased in NK cells of RA and SpA and in NKT and B cells of SpA patients compared to HC. The early activation marker CD69 was detected in all investigated PBMC subpopulations after 6h and 22h of stimulation with DR-agonists.
Conclusion: Our results show that TH and DRs are present on immune cells and their expression seems to be modulated on defined PBMC subpopulations in different rheumatic diseases. Reduced production of DA due to less synthesizing enzyme as well as hypersensitivity caused by increased DR expression may affect immune function and trigger inflammation. Further experiments are ongoing to better define the role of DA on peripheral immune cells during the course of the disease.
