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

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
• classically activated macrophages
• alternatively activated macrophages
• co-culture

ACKNOWLEDGEMENTS

We want to thank all participants of the study.

AUTHOR CONTRIBUTIONS

JY, JH, PY, and HL conceived and designed the experiments. JY, JH, LF, and SY performed all the experiments. ZY and AK reviewed data analysis and edited the manuscript. JY and JH contributed equally to this study.

DISCLOSURE OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

SUPPLEMENTAL DATA

Supplemental data for this article can be access on the publisher’s website.

Additional information

Funding

This work was support by National Natural Science Foundation Project (81470622); National Natural Science Foundation Project (81770913).