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

14 Citations (Scopus)

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 (US)
Pages (from-to)92-99
Number of pages8
JournalAutoimmunity
Volume41
Issue number1
DOIs
StatePublished - Feb 2008

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
Biliary Liver Cirrhosis
Autoimmunity
Antigen Presentation
Bile Ducts
Monocytes
Animal Disease Models
Regulatory T-Lymphocytes
Genetic Promoter Regions
Tryptophan
Single Nucleotide Polymorphism
Liver Diseases
T-Lymphocytes
Phenotype
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Impaired indoleamine 2,3-dioxygenase production contributes to the development of autoimmunity in primary biliary cirrhosis. / Oertelt-Prigione, Sabine; Mao, Tin; Selmi, Carlo; Tsuneyama, Koichi; Ansari, Aftab A.; Coppel, Ross L.; Invernizzi, Pietro; Podda, Mauro; Gershwin, M. Eric.

In: Autoimmunity, Vol. 41, No. 1, 02.2008, p. 92-99.

Research output: Contribution to journalArticle

Oertelt-Prigione, S, Mao, T, Selmi, C, Tsuneyama, K, Ansari, AA, Coppel, RL, Invernizzi, P, Podda, M & Gershwin, ME 2008, 'Impaired indoleamine 2,3-dioxygenase production contributes to the development of autoimmunity in primary biliary cirrhosis', Autoimmunity, vol. 41, no. 1, pp. 92-99. https://doi.org/10.1080/08916930701619730
Oertelt-Prigione, Sabine ; Mao, Tin ; Selmi, Carlo ; Tsuneyama, Koichi ; Ansari, Aftab A. ; Coppel, Ross L. ; Invernizzi, Pietro ; Podda, Mauro ; Gershwin, M. Eric. / Impaired indoleamine 2,3-dioxygenase production contributes to the development of autoimmunity in primary biliary cirrhosis. In: Autoimmunity. 2008 ; Vol. 41, No. 1. pp. 92-99.
@article{748aa3a335844065b446b3ca6ba7d71a,
title = "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-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.",
keywords = "Autoimmune cholangitis, Cellular immunity, Triptophan, Tumor growth factor",
author = "Sabine Oertelt-Prigione and Tin Mao and Carlo Selmi and Koichi Tsuneyama and Ansari, {Aftab A.} and Coppel, {Ross L.} and Pietro Invernizzi and Mauro Podda and Gershwin, {M. Eric}",
year = "2008",
month = "2",
doi = "10.1080/08916930701619730",
language = "English (US)",
volume = "41",
pages = "92--99",
journal = "Autoimmunity",
issn = "0891-6934",
publisher = "Informa Healthcare",
number = "1",

}

TY - JOUR

T1 - Impaired indoleamine 2,3-dioxygenase production contributes to the development of autoimmunity in primary biliary cirrhosis

AU - Oertelt-Prigione, Sabine

AU - Mao, Tin

AU - Selmi, Carlo

AU - Tsuneyama, Koichi

AU - Ansari, Aftab A.

AU - Coppel, Ross L.

AU - Invernizzi, Pietro

AU - Podda, Mauro

AU - Gershwin, M. Eric

PY - 2008/2

Y1 - 2008/2

N2 - 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.

AB - 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.

KW - Autoimmune cholangitis

KW - Cellular immunity

KW - Triptophan

KW - Tumor growth factor

UR - http://www.scopus.com/inward/record.url?scp=38049033923&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38049033923&partnerID=8YFLogxK

U2 - 10.1080/08916930701619730

DO - 10.1080/08916930701619730

M3 - Article

VL - 41

SP - 92

EP - 99

JO - Autoimmunity

JF - Autoimmunity

SN - 0891-6934

IS - 1

ER -