Neuroimmunology

Head:
Dr. rer. nat. med. habil. Silvia Capellino

The junior research group “Neuroimmunology” started in September 2016. Aim of this group is to study the effects of the nervous system on the immune system and on other peripheral cells.

Much clinical evidence suggests a direct interplay between the nervous system and the immune system. It is for example well known that stress and sleep disturbances increase the incidence of infectious diseases. This direct impact of the nervous system on our body is possible because immune cells and other peripheral cells express neurotransmitters’ receptors.

Although it is described that the nervous system directly influences our body’s immune response, we still do not know how this exactly works. Therefore, the Neuroimmunology group will work in cooperation with the other groups within the IfADo, in order to study the effects of the neurotransmitters on the immune response with a very interdisciplinary approach.

Aim of the group is to find out how exactly the nervous system acts on the immune system and on other organs in the physiological situation and during neurological and psychological diseases. This knowledge will allow to better treat patients and also to be aware of possible side effects of neuromodulating drugs on our immune response.

Furthermore, it was recently described that immune cells are able to produce neurotransmitters by themselves in some autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. These new findings open up a new field of research in immunology. We, therefore, plan to better characterize the neuronal-like mechanisms used by immune cells and to find out how we can use them to treat the above iseases with a very novel therapeutic approach.

Below you will find a short description of the ongoing projects.

 

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) as a model for bone erosion. Our first results confirm the involvement of dopamine on bone metabolism in RA.

Dopamine pathway seems to offer a promising new target for bone erosion in RA patients and potentially also in other pathologic conditions. 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 is funded by the European Commission, as Marie SkŁodowska-Curie Individual Fellowship within the Horizon2020 Program.

 

The dopamine pathway: a potential therapeutic target for local treatment of rheumatoid arthritis.

At present, treatment of rheumatoid arthritis (RA) aims to control inflammation by systemically suppressing the immune system and proinflammatory cytokines. Despite the great success of these treatments, side effects related to the systemic immunosuppression are still common. Thus, therapies that control the overactive immune response only in the inflamed synovial tissue would be preferable.

Recently, we described the production of dopamine by synovial cells in rheumatoid arthritis patients (Ann Rheum Dis 2010;69:1853–60). Receptors for dopamine were also expressed in inflamed synovial tissue, thus supporting the idea that locally produced neurotransmitters act in a paracrine/autocrine manner. Dopamine receptor expression is strongly upregulated selectively in RA synovial fibroblasts and dopamine treatment strongly inhibits IL-6 and IL-8 in vitro.

Based on these results, we hypothesize that dopamine-dependent pathways play a role in local immune response in RA patients. Moreover, as dopamine pathways are upregulated only in inflamed RA synovium, they represent potential targets for a specific and local therapy.

Therefore, the goal of the present study is to elucidate the mechanisms of action of dopamine in RA synovial fibroblasts, in order to define the best therapeutic target within the dopamine-regulated pathways and to determine the impact that such a therapeutic approach could have.