title: The innate immune system and inflammatory bowel disease.
abstract: The innate immune system is a key factor in understanding the pathogenesis of inflammatory bowel disease (IBD) and in the hopes of improving its treatment. NOD2, a pattern recognition receptor, was one of the first major susceptibility genes identified in Crohn's disease (CD). This discovery has been followed by genome-wide association studies that have identified other genes involved in innate immune responses. Most notably, polymorphisms in the interleukin (IL)-23 receptor have also been linked to IBD - both CD and ulcerative colitis. At the core of the innate immune defects associated with IBD is a lack of generating a robust response to control invasive commensal or pathogenic bacteria. The defect sometimes lies in a failure of the epithelium to express antimicrobial peptides or in defective control of intracellular bacteria by phagocytic cells such as dendritic cells, macrophages, or neutrophils. The recent identification of innate lymphoid cells that express the IL-23 receptor and generate both proinflammatory and protective or regulatory responses to commensal or pathogenic bacteria provides another layer of complexity to the interplay of host protection and dysregulated inflammation. Although inhibition of tumor necrosis factor has been highly successful as a strategy in treating IBD, we must better understand the nuanced role of other innate cytokines before we may incorporate these in the treatment of IBD.
authors.affiliation: Miller School of Medicine, University of Miami , Miami Fl , USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Davies
authors.forename: Maria T
authors.initials: MT
authors.lastname: Abreu
mesh_terms: D003713:Dendritic Cells / Q000276:immunology; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D020381:Interleukin-17 / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology; D010586:Phagocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology
chemical_list: D005819:Genetic Markers; D020381:Interleukin-17; D053759:Interleukin-23; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D051193:Toll-Like Receptors
keywords: Crohn’s disease; NOD-like receptors; Toll-like receptors; dendritic cells; inflammatory bowel disease; innate lymphoid cells; interleukin-17; interleukin-23; pattern recognition receptors; ulcerative colitis