title: Lymphocyte homing and its role in the pathogenesis of IBD.
abstract: Inflammatory bowel disease (IBD) is an idiopathic disorder of chronic inflammation of the gastrointestinal tract. Experimental models of IBD and results from human genomewide linkage studies suggest that the primary defect that leads to IBD is an inappropriate mucosal immune response to normal intestinal microbes. Genetic alterations not only confer increased susceptibility to IBD but also appear to determine the nature and location of the intestinal inflammation, as is evident in patients with genetic alterations of NOD2 and their susceptibility for ileal Crohn's disease. IBD has traditionally been classified into 2 subtypes, namely, ulcerative colitis (UC) and Crohn's disease (CD), based on histological appearance and anatomical distribution. However, an increasing body of data supports the concept that IBD is an umbrella diagnosis encompassing a variety of disorders with distinct genetic, microbial, and environmental determinants that cluster either into a UC or CD phenotype. The shared common pathway is uncontrolled intestinal inflammation. A key element in the pathogenesis of intestinal inflammation in both UC and CD is increased leukocyte recruitment from the circulation, and this provides a potential target for pharmaceutical inhibition. In this article we review the current understanding of the molecules that determine leukocyte trafficking to the gut and highlight opportunities where their inhibition could be exploited to treat IBD.(Inflamm Bowel Dis 2008).
authors.affiliation: Liver Research Laboratories, MRC Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Bertus
authors.initials: B
authors.lastname: Eksteen
authors.forename: Evaggelia
authors.initials: E
authors.lastname: Liaskou
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
mesh_terms: D003424:Crohn Disease / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology*