Inflammatory bowel disease: cause and immunobiology.
Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel disorders. In this paper, we discuss how environmental factors (eg, geography, cigarette smoking, sanitation and hygiene), infectious microbes, ethnic origin, genetic susceptibility, and a dysregulated immune system can result in mucosal inflammation. After describing the symbiotic interaction of the commensal microbiota with the host, oral tolerance, epithelial barrier function, antigen recognition, and immunoregulation by the innate and adaptive immune system, we examine the initiating and perpetuating events of mucosal inflammation. We pay special attention to pattern-recognition receptors, such as toll-like receptors and nucleotide-binding-oligomerisation-domains (NOD), NOD-like receptors and their mutual interaction on epithelial cells and antigen-presenting cells. We also discuss the important role of dendritic cells in directing tolerance and immunity by modulation of subpopulations of effector T cells, regulatory T cells, Th17 cells, natural killer T cells, natural killer cells, and monocyte-macrophages in mucosal inflammation. Implications for novel therapies, which are discussed in detail in the second paper in this Series, are covered briefly.
Baumgart
Daniel C
DC
Department of Medicine, Division of Gastroenterology and Hepatology, Charité Medical Centre, Virchow Hospital, Medical School of the Humboldt-University of Berlin, 13344 Berlin, Germany. daniel.baumgart@charite.de
Carding
Simon R
SR
D004781:Environmental Exposure / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007107:Immune System / Q000502:physiology*; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology; D007422:Intestines / Q000276:immunology; D007621:Karyotyping; D008019:Life Style; D053472:Nod Signaling Adaptor Proteins / Q000276:immunology / Q000502:physiology*; D015995:Prevalence; D012307:Risk Factors
D053472:Nod Signaling Adaptor Proteins