title: Role of defective autophagia and the intestinal flora in Crohn disease.
abstract: The precise mechanisms underlying the development of Crohn disease (CD) remain controversial, but sufficient data have been collected to suggest that an uncontrolled immune response within the intestinal mucosa leads to inflammation in a genetically susceptible host. Although lack of mucosal regulatory T cells causes colitis in humans and experimental rodents, patients with CD have more rather than less regulatory activity in the intestine, apparently excluding defects in tolerance as the cause of CD. Genome-wide association studies have identified many gene variants that confer susceptibility and which seem associated to diminished functioning of especially innate immunity. In apparent agreement, CD patients are impaired with respect to innate immune responses and controlling bacterial flora in the intestine. Furthermore, severe genetic deficiencies in innate immunity, like e.g., lack of NADP oxidase activity or diminished function of the Wiskott Aldrich syndrome protein are associated with colitis in mice and men, and are often mistakenly diagnosed as CD. Thus we favor the view that the primary defect in CD is a lack in innate immunity, causing second tier immunological defenses to combat otherwise easily controlled bacterial breaches of the mucosal barrier.
authors.affiliation: Diseases University Medical Center Groningen Hanzeplein 1 9713 GZ Groningen, The Netherlands.
authors.forename: Anouk
authors.initials: A
authors.lastname: Regeling
authors.affiliation: Department of Gastroenterology and Hepatology; Erasmus MC; University Medical Center Rotterdam; Rotterdam, The Netherlands.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Somasundaram
authors.affiliation: Department of Gastroenterology and Hepatology; Erasmus MC; University Medical Center Rotterdam; Rotterdam, The Netherlands.
authors.forename: Colin
authors.initials: C
authors.lastname: de Haar
authors.affiliation: Department of Gastroenterology and Hepatology; Erasmus MC; University Medical Center Rotterdam; Rotterdam, The Netherlands.
authors.forename: C Janneke
authors.initials: CJ
authors.lastname: van der Woude
authors.affiliation: Department of Gastroenterology and Hepatology; Erasmus MC; University Medical Center Rotterdam; Rotterdam, The Netherlands.
authors.forename: Henri
authors.initials: H
authors.lastname: Braat
authors.affiliation: Department of Gastroenterology and Hepatology; Erasmus MC; University Medical Center Rotterdam; Rotterdam, The Netherlands.
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch