The role of T‐regulatory cells and Toll‐like receptors in the pathogenesis of human inflammatory bowel disease

Abstract

SummaryTwo related chronic inflammatory diseases, Crohn's disease and ulcerative colitis, are together often referred to as inflammatory bowel disease (IBD). Current treatment options are not curative, and patients face lifelong therapy and debilitation. IBD is thought to be the product of a combination of genetic and environmental factors that result in the abnormal regulation of immune responses. Experimental models have demonstrated that normal CD4 + T-regulatory (Treg) cell responses and commensal bacteria are required for the maintenance of gut immune homeostasis. Recent evidence that CD4 + T cells express Toll-like receptors (TLRs) and respond directly to TLR ligands, suggests that signals from commensal bacteria may directly affect T-cell responses in the gut. In this review, we focus on evidence that defects in Treg cells may underlie IBD in humans. In addition, we discuss evidence that direct signaling via TLRs to T cells can affect IBD and that T-cell-dependent responses to bacterial proteins, such as flagellin, are central to the aetiology of this disease.

The role of intestinal alkaline phosphatase in pediatric inflammatory bowel and celiac diseases

“…A TLRcsalád 13 taggal rendelkezik, amelyeket az intestinalis epithelsejtek, miofi broblastok, enteroendokrin sejtek, valamin a bél lamina propria T-és dendritikus sejtjei expresszálnak. A TLR-ek extracelluláris doménje egy leucingazdag régióból, az intracelluláris komponens egy TIR (Toll/interleukin-1 receptor) doménből áll, amely az interleukin-1 receptor szupercsaláddal homológiát mutat [16,17].…”

Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics

“…Since the expression of TLR2 and TLR4 in both controls and asthmatics were mainly concentrated in CD4þCD25þ cells, we further assessed whether BUD affected the expression of TLR2 and TLR4 innate immune receptors in a subpopulation of CD4þCD25þ cells, i.e. on CD4þCD25highlyþ cells, the naturally occurring Treg [11,12]. We demonstrated that BUD increases the expression of both TLR2 and TLR4 in CD4þCD25highlyþ from recruited asthmatics but not from recruited controls.…”

“…The immunological mechanisms on the basis of the hygiene hypothesis are a missing immune deviation of allergen specific responses from a Th2 to a Th1 profile and a reduced activity of Treg cells [10]. Innate immunity receptors (TLRs) may directly modulate the suppressive activity of naturally occurring CD4(þ)CD25(highlyþ) Treg [11,12]. Accordingly, Treg cells are increased in farm-exposed children after LPS stimulation, the agonist of TLR4 [10].…”

“…Corticosteroids act on CD4þCD25þ cells from asthmatics increasing IL-10 production [12,18]. In CD4þ/CD25highlyþ cells from asthmatic patients BUD was able to increase the percentage of IL-10 positive cells (Fig.…”

“…Stimulation of innate immunity receptors can also directly influence the function of Treg cells. In this regard, it has been demonstrated that innate immunity receptors (TLRs) modulate the suppressive activity of naturally occurring CD4(þ)CD25(high) Treg [11,12].…”