The role of D2-like dopaminergic receptor in dopamine-mediated modulation of Th17-cells in multiple sclerosis

Abstract

: Dopamine is a direct mediator of neuroimmune interaction and may play a significant role in multiple sclerosis (MS) pathogenesis by modulating immune cell activity and cytokine production. We studied the effects of dopamine on Th17-cells function in 34 patients with relapsing-remitting MS and 23 healthy subjects. Production of interleukin-17 (IL-17), interferon-γ (IFN-γ), granulocyte-colony stimulating factor (GM-CSF), and IL-21 by CD4+ T-cells as well as dopamine were comparable between the groups. Dopamine suppressed IL-17, IFN-γ, GM-CSF, and IL-21 production by stimulated СD4+ T-cells in both groups. Blockade of D1-like dopaminergic receptor with a specific antagonist SCH23390 did not affect dopamine-mediated cytokine suppression. In contrast, blockade of D2-like dopaminergic receptor by sulpiride decreased dopamine's inhibitory effect on IL-17 secretion in both groups and GM-CSF and IL-21 production in MS patients. Blockade of D1-like dopaminergic receptor directly inhibited IL-17, IFN-γ, GM-CSF in both groups and IL-21 production in healthy subjects, while blockade of D2-like dopaminergic receptor had no effect on cytokine secretion. Finally, activation of D2-like dopaminergic receptor with a specific agonist quinpirole decreased IL-17, IFN-γ, and GM-CSF production in both groups. These data suggest an inhibitory role of dopamine on Th17-cells in MS, which could be mediated by the activation of D2-like dopaminergic receptor.