D1-Like Receptor Antagonist Inhibits IL-17 Expression and Attenuates Crescent Formation in Nephrotoxic Serum Nephritis

Abstract

Background/Aims: A dopamine type 1-like receptor (D1-like-R) expressed on dendritic cells was involved in Th17 cell differentiation of naive CD4⁺ T cells. Thus, we treated mice with nephrotoxic serum nephritis (NTN) with a D1-like-R antagonist to test whether Th17 cells play a role in this kidney disease. Methods: The SCH group of nephritic mice was administered with a D1-like-R antagonist, SCH23390, from day 0 to day 13. The kidney and spleen were collected at sacrifice on day 14. Glomerular pathology and CCR6⁺ cell infiltration were quantitatively evaluated. IL-4, IFN-γ and IL-17 mRNA levels in the kidney, and IFN-γ and IL-17 concentrations in the supernatants from splenocytes activated in vitro were measured. Results: Crescent formation had significantly developed in the positive control (PC) group of untreated, nephritic mice, which was suppressed in the SCH group. Glomerular infiltration of CCR6⁺ cells was also noted in the PC group, which was abolished in the SCH group. Renal IL-17 and IFN-γ mRNA levels were significantly reduced in the SCH group compared with the PC group. Additionally, in vitro activation augmented IFN-γ induction, but suppressed IL-17 induction by splenocytes from the SCH group compared with those from the PC group. Conclusion: We identified treatment with a D1-like-R antagonist inhibited IL-17 expression and attenuated crescent formation in NTN mice.