The Role Of TGR5 In Vogt-koyanagi-harada(VKH) Disease

Purpose:To investigate the role of G-protein-coupled bile acid receptor-1,Gpbar1(TGR5)in the pathogenesis of Vogt-Koyanagi-Harada(VKH)disease.Methods:The mRNA level of TGR5,iNOS,Arg1,CD16,and CD206in macrophages was assayed by real-time PCR.ELISA was used to detect the production of cytokines in cell culture supernatants.The frequencies of CD4~+IFN-γ~+and CD4~+IL-17~+T cells were tested by flow cytometry.Results:A decreased expression of of TGR5 in M1 macrophages was observed in active VKH patients as compared with normal controls.TGR5stimulation of M1 macrophages with INT-777 caused a shift of the inflammatory M1 towards to the anti-inflammatory M2 macrophage subtype.TGR5 activation of macrophages co-cultured with CD4~+T cells inhibited Th1 and Th17 polarization as well as the release of IFN-γand IL-17 in the culture supernatant.Conclusion:Our results show that a decreased TGR5 expression might contribute to the pathogenesis of VKH disease.