Antagonizing dopamine D1-like receptor inhibits Th17 cell differentiation: preventive and therapeutic effects on experimental autoimmune encephalomyelitis

Biochem Biophys Res Commun. 2008 Aug 22;373(2):286-91. doi: 10.1016/j.bbrc.2008.06.012. Epub 2008 Jun 17.


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 Galphas class of G proteins, while D2, D3 and D4 form the D2-like group that couples with the Galphai class of G proteins. A D2-like-receptor (D2-like-R) antagonist L750667 induced dendritic cell (DC)-mediated Th17 differentiation. In contrast, a D1-like-R antagonist SCH23390 inhibited DC-mediated Th17 differentiation. The D1-like-Rs were expressed on both DCs and T cells, whereas D2-like-Rs were marginally expressed on CD4+CD45RA+ naïve T cells. 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. Adoptive transfer of DCs treated with SCH23390 successfully prevented EAE. These findings indicate that antagonizing D1-like-Rs on DCs inhibits Th17 differentiation, thereby leading to an amelioration of EAE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Benzazepines / pharmacology
  • Benzazepines / therapeutic use*
  • Cell Differentiation / drug effects
  • Cell Polarity / drug effects
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control
  • Female
  • Humans
  • Interleukin-17 / metabolism
  • Lymphocyte Activation / drug effects
  • Mice
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Receptors, Dopamine D1 / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Benzazepines
  • Interleukin-17
  • L 750667
  • Pyridines
  • Pyrroles
  • Receptors, Dopamine D1