title: Paneth Cell Alterations in the Development and Phenotype of Crohn's Disease.
abstract: Pathogenesis of Crohn's disease (CD) involves immune and microbial dysregulation, induced by environmental factors in genetically susceptible individuals. There are believed to be multiple subtypes of CD, which contributes to its observed clinical heterogeneity. This concept has been reinforced by recognition of the complexity of the genetic, microbial, immune, and environmental factors that affect risk for CD. Paneth cells mediate immunity and maintain the small intestinal epithelium; defects in activities of these cells have been observed in high proportions of patients with CD, and are associated with a more aggressive CD phenotype. Paneth cells integrate complex genetic, immune, and environmental signals, therefore alterations in their function could lead to different subtypes of CD, as observed in studies in cohorts of primarily European descent. Subtypes of CD associated with Paneth cell function have been observed even among patients from different genetic backgrounds. We discuss genetic susceptibility loci for CD and how these affect Paneth cell activity.
authors.affiliation: Department of Pathology and Immunology, Washington University, Saint Louis, Missouri. Electronic address: stappenb@wustl.edu.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.affiliation: The F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Dermot P B
authors.initials: DPB
authors.lastname: McGovern
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000276:immunology; D000071183:Autophagy-Related Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D064806:Dysbiosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D019879:Paneth Cells / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype
chemical_list: C518959:ATG16L1 protein, human; C532820:Atg16l1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins
keywords: Autophagy; Crohn's Disease; Paneth Cell; Subtype