Indoleamine 2,3-Dioxygenase: Expressing Cells in Inflammatory Bowel Disease—A Cross-Sectional Study

Janette Furuzawa-Carballeda,Guadalupe Lima,Jesús K Yamamoto-Furusho,Gabriela Fonseca-Camarillo

doi:10.1155/2013/278035

Abstract

Aim. To characterise and enumerate IDO+ cells, Tregs, and T cell subsets in patients with ulcerative colitis (UC) and Crohn's disease (CD) with regard to their clinical activity. Methods. Ten active UC (aUC), 10 inactive UC (iUC), 6 aCD, and 8 iCD patients and 10 healthy individuals were included in the study. Circulating Foxp3-, IDO-, IL-17A-, IL-4-, IFN-γ-, and IL-10-expressing CD4+ T cells were quantitated by flow cytometry. Interleukin-17-expressing cells, CD25+/Foxp3+ Tregs, and CD123+/IDO+ plasmacytoid dendritic cells were evaluated in intestinal biopsies from 10 aUC, 6 aCD, and 10 noninflamed tissues. Results. All CD4+ T subsets were increased in aIBD patients compared with healthy donors. Meanwhile, frequency of CD8α +/CD16+/IDO+, CD8α +/CD56+/IDO+, CD8α +/CD80+/IDO+, CD8α +/CD123+/IDO+ large granular nonlymphoid cells, and CCR6+/CD123+/IDO+ plasmacytoid dendritic cells was higher in aIBD patients versus healthy donors or iIBD patients. Tissue IL-17A+ cells were present in higher amounts in aIBD versus noninflamed controls. IDO- and Foxp3-expressing cells were increased in aUC versus aCD patients and noninflamed tissues. Conclusions. The findings represent an original work in Mexican Mestizo patients with IBD. It shows that Tregs and IDO-expressing cells are increased with regard to disease activity. These cells could significantly shape inflammatory bowel disease pathophysiology, severity, and tolerance loss.

Highlights

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract
We studied a total of 44 individuals who were divided in five groups: active UC (aUC) (n = 10); inactive UC (iUC) (n = 10); active CD (aCD) (n = 6); inactive CD (iCD) (n = 8); healthy individuals (n = 10)
Tissue injury in IBD is thought to be primarily mediated by Th1 cells in CD or Th2 in UC [21], as we observed in our Mexican Mestizo patients

Summary

Introduction

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract. It is not preposterous to correlate the chronic relapsing inflammation with a tolerance dysregulation mechanism or an aberrant immune response to intestinal flora in a context of genetic predisposition [2]. In this vein, the catabolism of tryptophan, by the enzyme indoleamine 2,3-dioxygenase (IDO) expressed in plasmacytoid dendritic cells, generates kynurenines, 3-hydroxyanthranilic, and quinolic acids, molecules with the ability to exert cytotoxic action on T, B, and NK cells, but not on DCs themselves [3]. IDO-competent DCs have shown to induce CD4+/CD25hi regulatory T cells (Tregs) in vivo, and Tregexpressed glucocorticoid-induced tumour necrosis factor receptor (GITR) which in turn can use IDO+ DCs to expand their own population in a positive feedback loop [11, 12]

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