title: Rapid accumulation of CD14+CD11c+ dendritic cells in gut mucosa of celiac disease after in vivo gluten challenge.
abstract: BACKGROUND
  Of antigen-presenting cells (APCs) expressing HLA-DQ molecules in the celiac disease (CD) lesion, CD11c(+) dendritic cells (DCs) co-expressing the monocyte marker CD14 are increased, whereas other DC subsets (CD1c(+) or CD103(+)) and CD163(+)CD11c(-) macrophages are all decreased. It is unclear whether these changes result from chronic inflammation or whether they represent early events in the gluten response. We have addressed this in a model of in vivo gluten challenge.
  
  
  METHODS
  Treated HLA-DQ2(+) CD patients (n = 12) and HLA-DQ2(+) gluten-sensitive control subjects (n = 12) on a gluten-free diet (GFD) were orally challenged with gluten for three days. Duodenal biopsies obtained before and after gluten challenge were subjected to immunohistochemistry. Single cell digests of duodenal biopsies from healthy controls (n = 4), treated CD (n = 3) and untreated CD (n = 3) patients were analyzed by flow cytometry.
  
  
  RESULTS
  In treated CD patients, the gluten challenge increased the density of CD14(+)CD11c(+) DCs, whereas the density of CD103(+)CD11c(+) DCs and CD163(+)CD11c(-) macrophages decreased, and the density of CD1c(+)CD11c(+) DCs remained unchanged. Most CD14(+)CD11c(+) DCs co-expressed CCR2. The density of neutrophils also increased in the challenged mucosa, but in most patients no architectural changes or increase of CD3(+) intraepithelial lymphocytes (IELs) were found. In control tissue no significant changes were observed.
  
  
  CONCLUSIONS
  Rapid accumulation of CD14(+)CD11c(+) DCs is specific to CD and precedes changes in mucosal architecture, indicating that this DC subset may be directly involved in the immunopathology of the disease. The expression of CCR2 and CD14 on the accumulating CD11c(+) DCs indicates that these cells are newly recruited monocytes.
authors.affiliation: Centre for Immune Regulation and Department of Immunology, Oslo University Hospital - Rikshospitalet, Oslo, Norway. Ann-Christin.Beitnes@rr-research.no
authors.forename: Ann-Christin Røberg
authors.initials: AC
authors.lastname: Beitnes
authors.forename: Melinda
authors.initials: M
authors.lastname: Ráki
authors.forename: Margit
authors.initials: M
authors.lastname: Brottveit
authors.forename: Knut Erik Aslaksen
authors.initials: KE
authors.lastname: Lundin
authors.forename: Frode Lars
authors.initials: FL
authors.lastname: Jahnsen
authors.forename: Ludvig Magne
authors.initials: LM
authors.lastname: Sollid
mesh_terms: D000328:Adult; D000368:Aged; D039521:CD11c Antigen / Q000378:metabolism; D016022:Case-Control Studies; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology* / Q000473:pathology; D002452:Cell Count; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000473:pathology; D055050:Diet, Gluten-Free; D004386:Duodenum / Q000276:immunology / Q000473:pathology; D005260:Female; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006683:HLA-DQ Antigens / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology
chemical_list: D039521:CD11c Antigen; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; D005983:Glutens; D005903:Gliadin