The role of T-regulatory cells and Toll-like receptors in the pathogenesis of human inflammatory bowel disease.
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.
Himmel
Megan E
ME
Department of Surgery, University of British Columbia, and Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, Canada.
Hardenberg
Gijs
G
Piccirillo
Ciriaco A
CA
Steiner
Theodore S
TS
Levings
Megan K
MK
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D005408:Flagellin / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D018448:Models, Immunological; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
D000942:Antigens, Bacterial; D051193:Toll-Like Receptors; D005408:Flagellin
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