title: Defects in mucosal immunity leading to Crohn's disease.
abstract: Crohn's disease (CD) is characterized by patchy transmural inflammation involving any part of the intestinal tract. Animal models have provided a great deal of insight into the pathogenesis of CD, but no animal model has recapitulated the full spectrum of manifestations witnessed in human disease. The defects in mucosal immunity in CD can be divided into those that involve the epithelial barrier, those that involve the innate immune response, and finally, defects in the adaptive immune response. Defects in the epithelial barrier in CD include an increase in intestinal permeability, increased adherence of bacteria, and decreased expression of defensins. Murine and human studies have demonstrated an increased expression of T-helper 1 (Th1) cytokines by lamina propria lymphocytes. This increased Th1 cytokine expression is driven by interleukin-12 (IL-12)/IL-23 and tumor necrosis factor-like 1A (TL1A) production by antigen-presenting cells, resulting in Tbet expression by CD4+ T cells. Another dimension of the inappropriate immune response in CD is T-cell and B-cell reactivity to luminal microbes. With the identification of the nucleotide-binding oligomerization domain 2 (NOD2) gene as a susceptibility gene, defects in the innate immune response are beginning to be explored. One may consider a model in which defective innate immune clearance of pathogens or commensal bacteria in CD leads to an inappropriate adaptive immune response to the commensal flora.
authors.affiliation: Inflammatory Bowel Disease Center, Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Gena M
authors.initials: GM
authors.lastname: Cobrin
authors.forename: Maria T
authors.initials: MT
authors.lastname: Abreu
mesh_terms: D000818:Animals; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D018928:Immunity, Mucosal / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology*