Increased Expression of Indoleamine 2,3-Dioxygenase (IDO) in Vogt-Koyanagi-Harada (VKH) Disease May Lead to a Shift of T Cell Responses Toward a Treg Population

Liming Zhang, Yang Huang, Xiaoxiao Cui, Xiao Tan, Ying Zhu, Wenjun Zhou, Chaokui Wang, Gangxiang Yuan, Qingfeng Cao, Guannan Su, Aize Kijlstra, Peizeng Yang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Previous studies have pointed out that indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme initiating tryptophan metabolism, plays a role in the regulation of the immune system. This project was designed to investigate the potential role of IDO in monocyte-derived dendritic cells (moDCs) obtained from active Vogt-Koyanagi-Harada (VKH) disease patients. In this study, we found that the IDO mRNA expression and enzyme activity were increased in active VKH patients as compared with healthy controls and patients in remission. To investigate the role of IDO in immune regulation, an effective inhibitor 1-methyl-L-tryptophan (1-MT) was used to suppress its activity in DCs. The results showed that inhibition of IDO with 1-MT significantly decreased the expression of DC marker CD86. IDO inhibition did not affect the cytokine production of IL-6, IL-1β, TNF-α, IL-10, and TGF-β in DCs. Downregulation of IDO in DCs also led to the reduction of regulatory T (Treg) cells and an increased CD4 + T cell proliferation. Treatment with 1-MT did not affect the phosphorylation of the MAPK pathway in DCs. In general, our study suggests that IDO may play an important role in the pathogenesis of VKH disease by regulating DC and CD4 + T cell function. Tryptophan deficiency and kynurenine accumulation may account for the complicated effects of IDO. Further research is needed to study the precise tryptophan metabolites that may limit immune responses in VKH disease.

Original languageEnglish
Pages (from-to)1780-1788
Number of pages9
JournalInflammation
Volume43
Issue number5
DOIs
Publication statusPublished - Oct 2020

Keywords

  • Vogt-Koyanagi-Harada disease
  • IDO
  • tryptophan catabolism
  • dendritic cells
  • immune regulation
  • DENDRITIC CELLS
  • MATURATION
  • UVEITIS

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