title: Genetics and innate and adaptive immunity in IBD.
abstract: Inflammatory bowel disease (IBD) is an abnormal inflammatory response within the gut to a trigger that has yet to be identified. The family history in many patients, especially those with Crohn's disease, suggests a genetic predisposition. It has been hypothesized that the abnormal inflammatory response is due in part to genetic alterations in the normal homeostatic processes that regulate host interactions with the normal gut microbes. Genetic studies have identified increasing numbers of genetic risk factors that involve a diverse series of pathways such as receptors of innate immune response, defects in epithelial barrier function, immune- and cytokine-related genes and genes involved in autophagy. Studies further suggest that abnormal immune responses in IBD patients are directed against the intestinal microbiota, with activation of both innate and adaptive immune responses. Indeed, studies have shown bacterial-derived antigen as drivers of T cell immune responses. More recently, Th17, regulatory T cells and unconventional innate-like T cells have been implicated in the induction and regulation of intestinal inflammation. The seminal discoveries of pathogen recognition receptors including Toll-like receptors and nucleotide-binding oligomerization domain receptors have changed our understanding of how immune cells respond to microbes and the role this may play in IBD pathogenesis. Understanding these mechanism will lead to new strategies in the treatment and prevention of IBD.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Zane Cohen Center for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Galliano
authors.initials: G
authors.lastname: Zanello
authors.forename: David
authors.initials: D
authors.lastname: Kevans
authors.forename: Ashleigh
authors.initials: A
authors.lastname: Goethel
authors.forename: Mark
authors.initials: M
authors.lastname: Silverberg
authors.forename: Andrea
authors.initials: A
authors.lastname: Tyler
authors.forename: Kenneth
authors.initials: K
authors.lastname: Croitoru
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000276:immunology*; D007422:Intestines / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology