Neuroimmunology

DeBoRA: Dopamine and Bone Metabolism in Rheumatoid Arthritis

A few studies already exist, suggesting a direct link between dopamine and bone metabolism. However, nothing has been described so far about the role of dopamine and dopamine receptors (DRs) on pathologic bone resorption in humans.

We therefore perform experiments using rheumatoid arthritis (RA) – a chronic disease which causes inflammation and destruction of the joints – as a model for bone erosion. The main goal of this project is to identify the potential of dopamine pathway modulation in bone cells as therapeutic target towards a bone protective agent.

This project was started with funding of the European Commission, as Marie SkŁodowska-Curie Individual Fellowship within the Horizon2020 Program (2016-2018) and is conducted in cooperation with the Justus Liebig University Giessen and the Rheumazentrum Ruhrgebiet.

Disease-specific modulation of neurotransmitter-mediated pathways in immune cells

Previous studies reveal that the neurotransmitter dopamine contributes to local joint inflammation in RA. Moreover, it is demonstrated that dopamine can influence peripheral immune cells, and dopaminergic receptor expression is altered in peripheral immune cells in RA patients.

Based on these findings, we aim to investigate possible alterations of the dopaminergic pathway in peripheral immune cells in different rheumatic diseases: rheumatoid arthritis, psoriasis arthritis (PsA) and spondylitis ankylosans (SpA).

This project is conducted in cooperation with the Rheumazentrum Ruhrgebiet.

Stress leads to an activation of the sympathetic nervous system – part of the autonomic nervous system that regulates our body’s unconscious actions –  and to alteration of the immune response. We are interested in the direct effects of the sympathetic nervous system on the immune response during chronic and acute stress situations.

We are currently working on this topic in cooperation with other groups within IfADo and with colleagues from other universities.

It is described that the immune response changes during ageing. However, it is not known if neurotransmitter-mediated effects on the immune system are age-dependent or not. In cooperation with other groups within IfADo, we are therefore looking at age-dependent changes of the neuro-immune interaction.

Due to the fact that immune cells and other non-neuronal cells express neurotransmitter receptors and are able to synthesize neurotransmitters by themselves, one can assume that neuromodulating drugs can directly act on cells outside of the nervous system. Recent evidences confirm this hypothesis (Zhu et al 2017).

Our group is currently investigating the effects of dopaminergic drugs on non-neuronal cells. Dopaminergic drugs are directed to block the dopaminergic pathway (for example in Schizophrenia patients, where there is too much dopamine release) or to stimulate the dopaminergic pathway (like in Parkinson’s patients). Due to the fact that dopaminergic receptors are also present in cells outside of the central nervous system, these drugs could have unexpected effects in the body. A better knowledge of these interactions could be helpful for monitoring patients for possible side effects of dopaminergic drugs on the immune system. Moreover, better knowledge in this field could reveal future possibilities for the use of dopaminergic drugs in the treatment of non-neuronal disorders.