title: Lower expression of tight junction protein 1 gene and increased FOXP3 expression in the small bowel mucosa in coeliac disease and associated type 1 diabetes mellitus.
abstract: BACKGROUND
  The role of regulatory T cells expressing FOXP3 in the pathogenesis of coeliac disease (CD) and type 1 diabetes (T1D) has been reported. Recent data have placed special focus on the interplay between the intestinal barrier and immunoregulatory processes. We aimed to determine whether the expression of tight junction protein 1 (TJP1), which reflects small bowel mucosa permeability, is changed in CD and T1D.
  
  
  METHODS
  Transcription levels of TJP1 and FOXP3 genes were evaluated in the small bowel biopsies of 14 children with CD, 12 with CD and coexisting T1D and 40 controls using real-time PCR. Serum IgA and IgG to deamidated gliadin, bovine β-lactoglobulin, bovine α-casein and human tissue transglutaminase (tTG) were determined by ELISA.
  
  
  RESULTS
  The highest expression of FOXP3 mRNA was seen in patients with CD and T1D compared to patients with CD alone and controls (p = 0.02). In contrast, the lowest level of TJP1 mRNA expression was found in patients with CD and T1D (p = 0.01). The levels of IgA to deamidated gliadin and tTG were highest in patients with CD and T1D (p = 0.0001 and 0.01, respectively). The expression of FOXP3 mRNA correlated highly with the level of anti-gliadin IgA (p = 0.02) and anti-tTG IgA antibodies (p = 0.004).
  
  
  CONCLUSIONS
  The significant decline in TJP1 expression in CD patients, particularly in those with coexisting T1D, was accompanied by an increase in FOXP3 expression. This might reflect an attempt to maintain immune tolerance to counterbalance the loss of mucosal integrity in the small intestine in CD associated with T1D.
authors.affiliation: Institute of General and Molecular Pathology, Department of Immunology, University of Tartu, Ravila 19, Tartu, Estonia. tamara.vorobjova@kliinikum.ee
authors.forename: Tamara
authors.initials: T
authors.lastname: Vorobjova
authors.forename: Oivi
authors.initials: O
authors.lastname: Uibo
authors.forename: Ivi
authors.initials: I
authors.lastname: Ojakivi
authors.forename: Kaupo
authors.initials: K
authors.lastname: Teesalu
authors.forename: Marina
authors.initials: M
authors.lastname: Panarina
authors.forename: Kaire
authors.initials: K
authors.lastname: Heilman
authors.forename: Raivo
authors.initials: R
authors.lastname: Uibo
mesh_terms: D000293:Adolescent; D002446:Celiac Disease / Q000150:complications / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics* / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005786:Gene Expression Regulation; D005903:Gliadin / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D005903:Gliadin