Decreased Expression of TGR5 in Vogt-Koyanagi-Harada (VKH) Disease

  • Ocul Immunol Inflamm. 2020;28(2):200-208. doi: 10.1080/09273948.2018.1560477.
Jinglu Yang  1 ,  Jianping Hu  1 ,  Lujia Feng  1 ,  Shenglan Yi  1 ,  Zi Ye  1 ,  Meng Lin  1 ,  Xinglan Liu  1 ,  Yanyu Pu  1 ,  Aize Kijlstra  2 ,  Peizeng Yang  1 ,  Hong Li  1
Affiliations
  • 1. Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
  • 2. University Eye Clinic Maastricht, Maastricht, The Netherlands.
PMID: 30794473 DOI: 10.1080/09273948.2018.1560477
Abstract

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 CD206 in 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 TGR5 in M1 macrophages was observed in active VKH patients as compared with normal controls. TGR5 stimulation of M1 macrophages with INT-777 caused a shift of the inflammatory M1 toward 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-γ and IL-17 in the culture supernatant.Conclusion: Our results show that a decreased TGR5 expression might contribute to the pathogenesis of VKH disease.

Keywords
TGR5; VKH disease; alternatively activated macrophages; classically activated macrophages; co-culture.
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