Overexpression of indoleamine 2,3-dioxygenase in human inflammatory bowel disease

Anna Maria Wolf, Dominik Wolf, Holger Rumpold, Alexander R. Moschen, Arthur Kaser, Peter Obrist, Dietmar Fuchs, Gerald Brandacher, Christiane Winkler, Karel Geboes, Paul Rutgeerts, Herbert Tilg

Research output: Contribution to journalArticlepeer-review

Abstract

T-cells are causally involved in the pathogenesis of inflammatory bowel disease (IBD). The tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) regulates T-cell proliferation and survival. We show in this report that IDO mRNA is markedly induced in lesional colonic biopsies of IBD patients. IDO is primarily expressed in CD123+ mononuclear cells infiltrating the submucosal areas of the inflamed lesions. In Crohn's disease (CD), IDO is also strongly expressed in perifollicular regions of lymphoid follicles. Upregulation of IDO is of functional significance, as we detected an increase of kynurenine and of the kynurenine/tryptophan ratio in supernatants from colonic explant cultures (CECs) of CD patients. Immunohistochemistry of colonic biopsies taken from CD patients prior and after treatment with the TNF-blocking antibody Infliximab revealed reduced IDO expression in patients with good clinical response to Infliximab. In summary, high local expression of IDO may represent an anti-inflammatory mechanism tempting to counterbalance the tissue-damaging effects of activated T-cells infiltrating the colonic mucosa in IBD.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalClinical Immunology
Volume113
Issue number1
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

Keywords

  • CD
  • CEC
  • Colonic explant culture
  • Crohn's disease
  • DC
  • Dendritic cells
  • IBD
  • IDO
  • Immune regulation
  • Indoleamine 2,3-dioxygenase
  • Inflammation
  • Inflammatory bowel disease
  • Monoclonal antibody
  • mAb
  • qRT-PCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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