Five types of dopamine receptors, termed D1 to D5, have been identified to date. The D1 and D5 receptors form the D1-like group that couples with the Gαs class of G proteins, while D2, D3 and D4 form the D2-like group that couples with the Gαi class of G proteins. A D2-like-receptor (D2-like-R) antagonist L750667 specific for D4 induced dendritic cell (DC)-mediated Th17 differentiation. In contrast, a D1-like-R antagonist SCH23390 inhibited DC-mediated Th17 differentiation. The D1-like-R was expressed on DCs and T cells whereas D2-like-R, especially D4, was expressed on DCs alone. In addition, SCH23390 had the ability to prevent experimental autoimmune encephalomyelitis (EAE) in mice. Spleen cells from EAE mice showed decreased IL-17 production when SCH23390 was administered. The same effect of SCH23390 was observed in a diabetes model by using NOD mice. The CD4+ naive T cells stimulated by anti-CD3/CD28 Abs in the presence of dopamine markedly showed increased IL-17 secretion in a dose-dependent manner. These findings indicate that antagonizing D1-like receptors inhibits Th17 differentiation, thereby leading to an amelioration of autoimmunity.
Buy this Article