Antagonizing dopamine D1-like receptor inhibits Th17 cell differentiation: preventive and therapeutic effects on experimental autoimmune encephalomyelitis.
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.
Nakano
Kazuhisa
K
The Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Saitama 350-0495, Japan.
Higashi
Takehiro
T
Hashimoto
Kumiko
K
Takagi
Rie
R
Tanaka
Yoshiya
Y
Matsushita
Sho
S
D019264:Adoptive Transfer; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D001552:Benzazepines; D020381:Interleukin-17; C103081:L 750667; D011725:Pyridines; D011758:Pyrroles; D017447:Receptors, Dopamine D1