FIGURE 1 Proposed role of abnormal intestinal permeability in the pathogenesis of celiac disease.
From the following article:
Mechanisms of Disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases
Alessio Fasano and Terez Shea-Donohue
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Figure 1. Proposed role of abnormal intestinal permeability in the pathogenesis of celiac disease.
Gliadin and its immunomodulatory/inflammatory fragments are present in the intestinal lumen (1), which induces MyD88-dependent zonulin release (2). Zonulin release causes opening of tight junctions and gliadin passage across the tight junction barriers in subjects with dysregulation of the zonulin system (3). After tissue transglutaminase deamidation (4), gliadin peptides bind to human leukocyte antigen receptors present on the surface of antigen-presenting cells (5). Alternatively, gliadin can act directly on antigen-presenting cells (6), causing MyD88-dependent release of both zonulin and cytokines (7). Gliadin peptides are then presented to T lymphocytes (8), which process is followed by an aberrant immune response, both humoral (9) and cell-mediated (10), in genetically susceptible individuals. This interplay between innate and adaptive immunity is ultimately responsible for the autoimmune process targeting intestinal epithelial cells, leading to the intestinal damage typical of celiac disease (11). AEA, anti-endomysium antibodies; AGA, anti-gliadin antibodies; APC, antigen-presenting cell; 
tTG, anti-tissue transglutaminase; B, B lymphocyte; P, plasma cell; T, T lymphocyte; Tk, lymphocyte T killer; TTG, tissue transglutaminase.
