Innate immunity in inflammatory bowel disease: a disease hypothesis.
Crohn's disease arises from a defective interaction between the highly concentrated mass of bacteria in the gastrointestinal tract and the underlying tissues. It has generally been believed to result from an excessively exuberant inflammatory response or from 'autoimmunity'. Recent evidence has emerged that the problem is instead a failure of the way in which the body responds to the penetration of bacteria and other bowel contents through the intestinal mucosal barrier. Rather than Crohn's disease being caused by excessive inflammation, the primary mechanism is actually that of an immunodeficiency. Failure of inflammatory mediator production leads to insufficient recruitment of neutrophils, resulting in inadequate removal of bacteria and other debris. This impairment of acute inflammation can be compensated in some circumstances by signalling through NOD2. If not cleared, the foreign material in the bowel wall is taken up within macrophages, eliciting a granulomatous reaction and the local and systemic sequelae so characteristic of Crohn's disease.
Marks
D J B
DJ
Centre for Molecular Medicine, University College London, UK.
Segal
A W
AW
D000208:Acute Disease; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D009504:Neutrophils / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000502:physiology
D005765:Gastrointestinal Agents; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein