Role of defective autophagia and the intestinal flora in Crohn disease
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.
|Keywords||ATG16, Crohn disease, GWAS, IL10, IRGM, NOD2, Tregs, Ulcerative colitis, Wiskott Aldrich syndrome protein, article, autophagy, colitis, diagnostic error, disease course, enzyme activity, experimental mouse, gastrointestinal mucosa, genetic association, genetic disorder, genetic susceptibility, genetic variability, human, immune response, immunological tolerance, inflammation, innate immunity, intestine flora, intestine mucosa, molecular mechanics, nonhuman, reduced nicotinamide adenine dinucleotide phosphate oxidase, regulatory T lymphocyte|
|Persistent URL||dx.doi.org/10.4161/self.1.4.13990, hdl.handle.net/1765/22990|
Leshed, A., Somasundaram, R., de Haar, C., van der Woude, C.J., Braat, H., & Peppelenbosch, M.P.. (2010). Role of defective autophagia and the intestinal flora in Crohn disease. Self Nonself, 1(4), 323–327. doi:10.4161/self.1.4.13990