Content area
Full Text
About the Authors:
Alexander Lee
Contributed equally to this work with: Alexander Lee, Navya Kanuri
Affiliation: Division of Gastroenterology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America
Navya Kanuri
Contributed equally to this work with: Alexander Lee, Navya Kanuri
Affiliation: Division of Gastroenterology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America
Yuanhao Zhang
Affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, United States of America
Gregory S. Sayuk
Affiliations Division of Gastroenterology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America, Division of Gastroenterology, Veteran Affairs Medical Center, John Cochrane Division, St. Louis, Missouri, United States of America
Ellen Li
Affiliation: Division of Gastroenterology, Stony Brook University, Stony Brook, New York, United States of America
Matthew A. Ciorba
* E-mail: [email protected]
Affiliation: Division of Gastroenterology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America
Introduction
Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) affecting of millions of people of all races worldwide. Current evidence suggests that CD occurs in genetically susceptible individuals who develop loss of tolerance and a resultant chronic immune response against commensal luminal microbiota, likely in response to an antecedent environment trigger. [1], [2] Genome wide association studies (GWAS) have identified over a hundred and sixty genetic loci and non-synonymous single nucleotide gene variants (SNPs) which associate with risk of developing CD. [3] Many of these genes relate to microbial defense mechanisms, epithelial barrier function and the innate and adaptive immune systems. [4] However, less than 15% of CD variance is explained by these genes [3] and many genes may impact disease phenotype or severity rather than influence disease risk.
Indoleamine 2,3 dioxygenase-1 (IDO1) is a widely expressed enzyme which is the initial and rate limiting step of tryptophan catabolism along the kynurenine pathway. IDO1 expression is inducible by inflammatory stimuli including cytokines and toll like receptor agonists. The resulting suppression of local tryptophan and increase in bioactive kynurenine pathway metabolites functions to reduce inflammation and promote immune tolerance via several mechanisms. [5] Among these include exertion of antimicrobial activity, suppression of activated T-cell responses and induction of...