The dopaminergic system in autoimmune diseases. Frontiers in Immunology2/05/2014
ABSTRACT: Bidirectional interactions between the immune and the nervous system sare of considerable interest both for deciphering their functioning and for designing novel therapeutic strategies. The past decade has brough taburs to finsights into the molecular mechanisms involvedin neuroimmune communications mediated by dopamine. Studies of dendritic cells (DCs) revealed that they express the whole machinery to synthesize and store dopamine, which may act in an autocrine manner to stimulate dopamine receptors (DARs). Depending on specific DARs stimulate do nDCs and T cells,dopamine may differentially favor CD4+ T cell differentiation into Th1 or Th17 inflammatory cells. Regulatory T cell scan also release high amounts of dopamine that acts in an autocrine DAR-mediated manner to inhibit heir suppressive activity. These dopaminergic regulations could represent a driving force during autoimmunity. Indeed, dopamine levels are altered in the brain of mouse models of multiples clerosis (MS) andl upus, and ininflamed tissues of patients with inflammatory bowel diseases or rheumatoid arthritis (RA). The distorted expression of DAR in peripheral lymphocytes of lupus and MS patients also supports the importance of dopaminergic regulations in automunity. More over, dopamine analogs had beneficial therapeutic effects in animal models,and in patients with lupus or RA. We propose models that may underlie key roles of dopamine and its receptors in autoimmune diseases.