title: In the Intestinal Mucosa of Children With Potential Celiac Disease IL-21 and IL-17A are Less Expressed than in the Active Disease.
abstract: OBJECTIVE
  Potential celiac disease (CD) patients are at an increased risk to developing CD as indicated by positive CD-associated serology. We investigated in duodenal mucosa of such patients the presence of both IL-21 and IL-17A and the role of gliadin peptides and IL-15 in their expression.
  
  
  METHODS
  Duodenal biopsies from 76 active CD, 90 potential CD, and 58 control patients were analyzed for IL-21 and/or IL-17A production by quantitative real-time PCR, immunohistochemistry, flow cytometry, and ELISA. The presence of IL-21 receptor was investigated by western blot. Potential CD duodenal fragments were cultured with gliadin peptides (PTG) and/or IL-15 and the expression/production of IL-21 and IL-17A assessed by quantitative real-time PCR and by immunohistochemistry.
  
  
  RESULTS
  In potential CD, IL-21 was lower than in active CD, in terms of RNA expression (P<0.01), density of lamina propria (LP) IL-21(+) cells (P<0.05), and protein secretion (P<0.05). Also, IL-21R was weakly detectable in potential CD. Several LP cell types produced IL-21 in CD. In potential CD, CD4(+)IL-21(+) cells increased after PMA-ionomycin stimulation and co-produced IFN-γ but not IL-17A. After 24 hours of culture stimulation with PTG, IL-21-producing cells increased but not the ones producing IL-17A. This increase was further enhanced by the addition of IL-15 to culture medium.
  
  
  CONCLUSIONS
  In potential CD, IL-21 is less expressed than in active CD; however, IL-21-producing cells are present and prone to respond after specific stimuli. This suggests a key role of IL-21 in the progression of mucosal damage in CD.
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: Borrelli
authors.affiliation: Institute of Protein Biochemistry, CNR, Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gianfrani
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Lania
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Rosita
authors.initials: R
authors.lastname: Aitoro
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Ferrara
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Merlin
authors.initials: M
authors.lastname: Nanayakkara
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ponticelli
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Zanzi
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Discepolo
authors.affiliation: Institute of Protein Biochemistry, CNR, Naples, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Vitale
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Barone
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Troncone
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Auricchio
authors.affiliation: Department of Pediatrics, European Laboratory for the Investigation of Food-Induced Diseases, University Federico II, Naples, Italy.
authors.forename: Mariantonia
authors.initials: M
authors.lastname: Maglio
mesh_terms: D002446:Celiac Disease / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004386:Duodenum / Q000378:metabolism; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D000098546:Interleukin-21
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D007378:Interleukins; D000098546:Interleukin-21