The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease - PubMed (original) (raw)

Review

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

Megan E Himmel et al. Immunology. 2008 Oct.

Abstract

Two 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.

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Figures

Figure 1

Figure 1

Model for how flagellin could influence the balance between T–effector (Teff) and T-regulatory (Treg) cells in inflammatory bowel disease (IBD). Increased epithelial permeability associated with IBD could result in abnormal exposure of cells in the lamina propria to flagellin from commensal bacteria. Flagellin could be phagocytosed and presented as an antigen by dendritic cells (DCs) to CD4+ T cells. In parallel, flagellin could stimulate Toll-like receptor 5 (TLR-5) on immune and non-immune cells to induce maturation, proliferation and cytokine production. Depending on the concentration, and on other inflammatory signals, flagellin could thereby alter the balance between Treg and Teff cells. Other TLR ligands from commensal bacteria may also directly stimulate TLRs on T cells and contribute to the overall effect. FL, flagellin; FOXP3, forkhead box P3; MHC, major histocompatibility complex; TCR, T-cell receptor.

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