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

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

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14 Citations (Scopus)


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-gamma 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-beta 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
Issue number1
Publication statusPublished - 2008

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