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Tight Junctions, Intestinal Permeability, and Autoimmunity
Author(s) -
Visser Jeroen,
Rozing Jan,
Sapone Anna,
Lammers Karen,
Fasano Alessio
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.04037.x
Subject(s) - autoimmunity , immunology , enteropathy , intestinal permeability , gliadin , genetic predisposition , pathogenesis , autoimmune disease , immune system , human leukocyte antigen , type 1 diabetes , biology , disease , gluten , medicine , genetics , antigen , diabetes mellitus , gene , antibody , endocrinology , food science , pathology
Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type 1 diabetes (T1D), a hyperglycosaemia caused by a destructive autoimmune process targeting the insulin‐producing pancreatic islet cells. Even if environmental factors and genetic susceptibility are clearly involved in the pathogenesis of autoimmunity, for most autoimmune disorders there is no or little knowledge about the causing agent or genetic makeup underlying the disease. In this respect, CD represents a unique autoimmune disorder because a close genetic association with HLA‐DQ2 or HLA‐DQ8 haplotypes and, more importantly, the environmental trigger (the gliadin fraction of gluten‐containing grains wheat, barley, and rye) are known. Conversely, the trigger for autoimmune destruction of pancreatic ß cells in T1D is unclear. Interestingly, recent data suggest that gliadin is also involved in the pathogenesis of T1D. There is growing evidence that increased intestinal permeability plays a pathogenic role in various autoimmune diseases including CD and T1D. Therefore, we hypothesize that besides genetic and environmental factors, loss of intestinal barrier function is necessary to develop autoimmunity. In this review, each of these components will be briefly reviewed.