Dopamine suppresses Th17-cells function in multiple sclerosis

Young Investigator
Mikhail Melnikov
57
Moscow, Russia

Abstract

Introduction:
Dopamine may participate in multiple sclerosis (MS) pathogenesis by modulating immune cell activity and cytokine production. This study aimed to clarify the effect of dopamine on Th17-cells, which plays a critical role in MS pathogenesis.

Methods:
Forty patients with relapsing-remitting MS during clinical remission and twenty-five healthy subjects were examined. The concentrations of dopamine in blood plasma and culture supernatants were measured by high-performance liquid chromatography. The percentage of blood Th17-cells was determined by flow cytometry (CD4+CD161+). To assess the effect of dopamine on Th17-cells, purify CD4+-T-cells were cultured in the presence of dopamine (10–5 M) and stimulated with anti-CD3/anti-CD28-antibodies. The levels of IL-17, IFN-γ, and GM-CSF in culture supernatants were assessed by ELISA. To study the involvement of dopaminergic receptors in dopamine-mediated immunomodulation, some samples of CD4+-T-cells were pre-incubated with antagonist of D1- or D2-dopaminergic receptors, whereafter dopamine and anti-CD3/anti-CD28-antibodies were added to the cultures. In some experiments, CD4+-T-cells were pre-incubated with antagonist of D1- or D2-dopaminergic receptors (both at 10–5 M) and activated by anti-CD3/anti-CD28-antibodies.

Results:
The concentrations of dopamine in plasma and culture supernatants were not different between the groups. The percentages of Th17-cells, as well as the production of cytokines, were also comparable. Dopamine suppressed cytokine production in both groups (p<0.0001) without affecting on cell viability and proliferative response. Blockade of D1-receptors enhanced the inhibitory effect of dopamine on cytokine production in both groups (p<0.05), while blockade of D2-receptors decreased the inhibitory effect of dopamine in both groups (p<0.05). The blockade of D1-receptors suppressed cytokine production in both groups (p<0.01).

Conclusion:
These data suggest the inhibitory effect of dopamine on Th17-cells in MS, which could be mediated by the D2-dopaminergis receptors.

Dopamine suppresses Th17-cells function in multiple sclerosis

M. Melnikov 1–3 (main author), A. Sviridova 1, M. Pashenkov 3, A. Boyko 1,2.
1 Federal Center of Brain research and Neurotechnology of the Federal Medical Biological Agency of Russia, Department of Neuroimmunology, Moscow, Russia 2 Pirogov Russian National Research Medical University, Department of Neurology, Neurosurgery and Medical Genetics, Moscow, Russia
3 National Research Center Institute of Immunology of the Federal Medical Biological Agency of Russia, Laboratory of Clinical Immunology, Moscow, Russia