title: Immunopathogenesis of inflammatory bowel disease: current concepts.
abstract: OBJECTIVE
  According to the current paradigm, ulcerative colitis and Crohn's disease occur in genetically predisposed individuals because of dysregulated immune responses against intraluminal bacterial antigens. Data have recently accumulated supporting alternative hypotheses for the pathogenesis of inflammatory bowel disease. Here, we present novel immunogenetic pathways and discuss their impact on traditional understanding of inflammatory bowel disease.
  
  
  RESULTS
  In the gastrointestinal tract the innate immune system contains intraluminal bacteria locally, avoiding invasion of the deeper layers and preventing induction of long-standing proinflammatory responses. Failure of this protective function of the innate immune system appears to be the primary defect in inflammatory bowel disease, as a result of impairment of NOD2 signaling or other unidentified deficiencies. The adaptive immune response that ensues was thought to be strictly differentiated between T-helper-1 mediated in Crohn's disease and T-helper-2 mediated in ulcerative colitis. This concept is rapidly changing, however, in light of recent evidence suggesting that tissue injury in inflammatory bowel disease is mediated by novel effector pathways, the most prominent of which is the interleukin-23/Th17 axis.
  
  
  CONCLUSIONS
  Elucidation of the pathways that underlie chronic intestinal inflammation will facilitate the development of new treatments with increased specificity and probably with decreased toxicity.
authors.affiliation: First Department of Propaedeutic Medicine, Laiko General Hospital, Athens, Greece, and Digestive Health Center of Excellence, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
authors.forename: Giorgos
authors.initials: G
authors.lastname: Bamias
authors.forename: Fabio
authors.initials: F
authors.lastname: Cominelli
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin