title: Celiac Disease: Role of the Epithelial Barrier.
abstract: In celiac disease (CD) a T-cell-mediated response to gluten is mounted in genetically predisposed individuals, resulting in a malabsorptive enteropathy histologically highlighted by villous atrophy and crypt hyperplasia. Recent data point to the epithelial layer as an under-rated hot spot in celiac pathophysiology to date. This overview summarizes current functional and genetic evidence on the role of the epithelial barrier in CD, consisting of the cell membranes and the apical junctional complex comprising sealing as well as ion and water channel-forming tight junction proteins and the adherens junction. Moreover, the underlying mechanisms are discussed, including apoptosis of intestinal epithelial cells, biology of intestinal stem cells, alterations in the apical junctional complex, transcytotic uptake of gluten peptides, and possible implications of a defective epithelial polarity. Current research is directed toward new treatment options for CD that are alternatives or complementary therapeutics to a gluten-free diet. Thus, strategies to target an altered epithelial barrier therapeutically also are discussed.
authors.affiliation: Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schumann
authors.affiliation: Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Siegmund
authors.affiliation: Institute of Clinical Physiology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Schulzke
authors.affiliation: Institute of Clinical Physiology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fromm
keywords: Bmp, bone morphogenetic protein; CBC, crypt base columnar cell; CD, celiac disease; Celiac Sprue; EGF, epidermal growth factor; Epithelial Polarity; GFD, gluten-free diet; GI, gastrointestinal; GWAS, genome-wide association studies; Gluten-Sensitive Enteropathy; IEC, intestinal epithelial cell; IL, interleukin; MIC-A, major histocompatibility complex class I chain–related gene-A; Partitioning-Defective Proteins; SNP, single-nucleotide polymorphism; TJ, tight junction; Tight Junction; ZO, zonula occludens; aPKC, atypical protein kinase C; α-Gliadin 33mer