Indoleamine 2,3 dioxygenase in intestinal disease

Abstract

Several gastrointestinal diseases including the inflammatory bowel diseases (IBDs) and malignancy are associated with elevated expression of indoleamine 2,3 dioxygenase-1 (IDO1). IDO1 initiates tryptophan catabolism along a pathway that generates several bioactive kynurenine-based metabolites. Promotion of T-cell-mediated tolerance and antimicrobial effects are among the variety of functions attributed to IDO1 activity. Recent advances addressing the diverse implications of gut-associated IDO1 expression are herein reviewed. In active IBD, IDO1 is highly expressed both in the cells of the lamina propria and epithelium. Experimental models demonstrate that IDO1 promotes gut immune homeostasis by limiting inflammatory responses and protecting the epithelium. In human colon cancer, high expression of IDO1 by the neoplastic epithelium correlates with poor prognosis. The serum kynurenine : tryptophan ratio is elevated in both active Crohn's disease and in colon cancer, suggesting this measurement may prove useful as a disease biomarker. IDO1 inhibitors have moved to clinical trials providing new hope as immunotherapy for advanced malignancy. IDO1 activity significantly shapes gastrointestinal disease pathophysiology and severity. Measures of IDO1 activity may be useful as a disease biomarker. Manipulation of IDO1 activity has great potential as a treatment for both inflammatory and malignancy associated gastrointestinal disease.