Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms

Jeroen Visser, Jan Rozing, Anna Sapone, Karen Lammers, Alessio Fasano*

*Corresponding author for this work

    Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

    198 Citations (Scopus)

    Abstract

    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 I diabetes (TID), 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 beta cells in TID is unclear. Interestingly, recent data suggest that gliadin is also involved in the pathogenesis of TID. There is growing evidence that increased intestinal permeability plays a pathogenic role in various autoimmune diseases including CD and TID. 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.

    Original languageEnglish
    Title of host publicationMOLECULAR STRUCTURE AND FUNCTION OF THE TIGHT JUNCTION: FROM BASIC MECHANISMS TO CLINICAL MANIFESTATIONS
    EditorsM Fromm, JD Schulzke
    Place of PublicationOXFORD
    PublisherBlackwell Publishing
    Pages195-205
    Number of pages11
    ISBN (Print)978-1-57331-749-8
    DOIs
    Publication statusPublished - 2009
    EventConference on Molecular Structure and Function of the Tight Junction - From Basic Mechanisms to Clinical Manifestations - , Germany
    Duration: 25-Apr-200827-Apr-2008

    Publication series

    NameANNALS OF THE NEW YORK ACADEMY OF SCIENCES
    PublisherBLACKWELL PUBLISHING
    Volume1165
    ISSN (Print)0077-8923

    Other

    OtherConference on Molecular Structure and Function of the Tight Junction - From Basic Mechanisms to Clinical Manifestations
    Country/TerritoryGermany
    Period25/04/200827/04/2008

    Keywords

    • tight junctions
    • intestinal permeability
    • zonulin
    • celiac disease
    • type 1 diabetes
    • gliadin
    • ZONULA OCCLUDENS TOXIN
    • PRONE BB RAT
    • HUMORAL IMMUNITY
    • GUT PERMEABILITY
    • BARRIER FUNCTION
    • VIBRIO-CHOLERAE
    • CELL LINES
    • GLIADIN
    • BINDING
    • MUCOSA

    Cite this