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

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-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.

journal_name

Autoimmunity

journal_title

Autoimmunity

authors

Oertelt-Prigione S,Mao TK,Selmi C,Tsuneyama K,Ansari AA,Coppel RL,Invernizzi P,Podda M,Gershwin ME

doi

10.1080/08916930701619730

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

92-9

issue

1

eissn

0891-6934

issn

1607-842X

pii

789170278

journal_volume

41

pub_type

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