title: Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation in celiac disease.
abstract: OBJECTIVE
  The aim was to investigate the mucosal activation of a broad range of genes associated with the T-helper 17 cell (Th17) signaling pathway in children at different stages of celiac disease (CD), including children with increased risk for CD and children with untreated and gluten-free diet (GFD)-treated CD.
  
  
  METHODS
  Small intestinal biopsies were taken from children with untreated and GFD-treated CD, transglutaminase antibody (TGA)-positive children with potential CD, and reference children. Real-time polymerase chain reaction (PCR) arrays were used to study the gene expression pattern of Th17-related genes, and quantitative PCR was used to study the interleukin (IL)-17A expression.
  
  
  RESULTS
  The mucosal expression of CD8A was elevated at all stages of CD. Children with untreated CD had diminished levels of IL-17RE, IL-23R, RORc, STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and matrix metalloproteinase (MMP)9 but had elevated levels of MMP3, IL-17, interferon-γ (IFN-γ) and CD8A, compared to references. The majority of the aforementioned genes, being differentially expressed in untreated CD, displayed similar expression in GFD-treated children and references. Children with untreated and GFD-treated CD had elevated expression of IFN-γ but had reduced expression of CD247. Interestingly, children with potential CD displayed reduced FOXP3, IL-21, and IL-17A levels.
  
  
  CONCLUSIONS
  Mucosal upregulation of Th17 immunity occurs at the late stage of disease and is downregulated with dietary treatment, thus indicating that IL-17 immunity is not a fundamental feature of CD as Th1 immunity, which is not fully downregulated by GFD.
authors: Department of Clinical and Experimental Medicine, Division of Paediatrics, Faculty of Health Sciences, Linköping University , Linköping , Sweden.
authors: Anne I
authors: AI
authors: Lahdenperä
authors: Karin
authors: K
authors: Fälth-Magnusson
authors: Lotta
authors: L
authors: Högberg
authors: Johnny
authors: J
authors: Ludvigsson
authors: Outi
authors: O
authors: Vaarala
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000097:blood; D015703:Antigens, CD / Q000235:genetics*; D016022:Case-Control Studies; D002446:Celiac Disease / Q000178:diet therapy / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004751:Enteritis / Q000235:genetics / Q000276:immunology; D005260:Female; D019204:GTP-Binding Proteins; D015870:Gene Expression; D006801:Humans; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D018123:Receptors, Interleukin / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D058504:Th17 Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D011503:Transglutaminases / Q000276:immunology
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D036341:Intercellular Signaling Peptides and Proteins; D018123:Receptors, Interleukin; D014157:Transcription Factors; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D019204:GTP-Binding Proteins