Liver Cirrhosis Research Today is a free monthly online journal that collates and summarizes the latest research about Liver Cirrhosis, including details on alcohol, treatment, drugs, effects, causes.

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

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

Division of Rheumatology, Allergy, and Clinical Immunology, University of California at Davis, Davis, CA 95616, USA.

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.

Published 7 January 2008 in Autoimmunity, 41(1): 92-9.
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