Impaired indoleamine 2,3-dioxygenase production contributes to the development of autoimmunity in primary biliary cirrhosis

Sabine Oertelt-Prigione, Tin Mao, Carlo Selmi, Koichi Tsuneyama, Aftab A. Ansari, Ross L. Coppel, Pietro Invernizzi, Mauro Podda, M. Eric Gershwin

Research output: Contribution to journalArticle

Abstract

The immunomodulatory effects of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been elucidated at a cellular level and implicated in the pathogenesis of several complex diseases. Defects within the regulatory T cell compartment are one of the characteristics of primary biliary cirrhosis (PBC), an autoimmune chronic cholestatic liver disease, a phenotype that has also been shown in disease-mimicking animal models of this disease. We hypothesized that IDO dysregulation could lead to altered frequency and/or function of T cells at the level of antigen processing/presentation and we thus investigated IDO in peripheral monocytes and bile duct cells from patients with PBC. Both expression and activation manifested an impaired IFN-γ response in peripheral monocytes while a peculiar IDO expression profile in bile duct cells characterized early stage PBC. Further, we observed an increased frequency of a gain-of-function SNP within the TGF-β promoter region, a molecule known to suppress IDO transcription. In conclusion, we submit that an impaired IDO induction characterizes PBC and might represent a contributing factor in disease pathogenesis in association with several specific defects in the target tissue.

Original languageEnglish
Pages (from-to)92-99
Number of pages8
JournalAutoimmunity
Volume41
Issue number1
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Autoimmune cholangitis
  • Cellular immunity
  • Triptophan
  • Tumor growth factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Oertelt-Prigione, S., Mao, T., Selmi, C., Tsuneyama, K., Ansari, A. A., Coppel, R. L., Invernizzi, P., Podda, M., & Gershwin, M. E. (2008). Impaired indoleamine 2,3-dioxygenase production contributes to the development of autoimmunity in primary biliary cirrhosis. Autoimmunity, 41(1), 92-99. https://doi.org/10.1080/08916930701619730