Overexpression of indoleamine 2,3-dioxygenase in human inflammatory bowel disease.
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.
Wolf
Anna Maria
AM
Department of Medicine, Division of Gastroenterology and Hepatology, University Hospital Innsbruck, Internal Medicine, Innsbruck, Austria.
Wolf
Dominik
D
Rumpold
Holger
H
Moschen
Alexander R
AR
Kaser
Arthur
A
Obrist
Peter
P
Fuchs
Dietmar
D
Brandacher
Gerald
G
Winkler
Christiane
C
Geboes
Karel
K
Rutgeerts
Paul
P
Tilg
Herbert
H
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D000069285:Infliximab; D053650:Interleukin-3 Receptor alpha Subunit; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D000949:Histocompatibility Antigens Class II; C115022:IL3RA protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053650:Interleukin-3 Receptor alpha Subunit; D012333:RNA, Messenger; D016185:Receptors, Interleukin-3; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D014366:Tryptophan Oxygenase