title: Enteroendocrine cells in terminal ileal Crohn's disease.
abstract: OBJECTIVE
  Enteroendocrine cells sense gut luminal contents, and orchestrate digestive physiology whilst contributing to mucosal homeostasis and innate immunity. The terminal ileum is the key site of EEC expression but detailed assessment of their subtypes, lineage transcription factors and expression products has not been undertaken in terminal ileal Crohn's disease. Recent Crohn's disease gene wide association studies have linked the neuroendocrine transcription factor Phox2b; while autoantibodies to an enteroendocrine protein, ubiquitination protein 4a, have been identified as a disease behaviour biomarker.
  
  
  METHODS
  Terminal ileal tissue from small or large bowel Crohn's disease and normal controls was analysed for enteroendocrine marker expression by immunohistochemistry and quantitative polymerase chain reaction. Inflammation was graded by endoscopic, clinical, histological and biochemical scoring.
  
  
  RESULTS
  In small bowel disease, glucagon-like peptide 1 and chromogranin A cells were increased 2.5-fold (p=0.049) and 2-fold (p=0.031) respectively. Polypeptide YY cells were unchanged. Ileal enteroendocrine cell expression was unaffected in the presence of Crohn's colitis. Phox2b was co-localised to enteroendocrine cells and showed a 1.5-fold increase in ileal disease. Significant mRNA increases were noted for chromogranin A (3.3-fold; p=0.009), glucagon-like peptide 1 (3.1-fold; p=0.007) and ubiquitination protein 4a (2.2-fold; p=0.02). Neurogenin 3, an enteroendocrine transcription factor showed ~2 fold-upregulation (p=0.048).
  
  
  CONCLUSIONS
  Enhanced enteroendocrine cell activity is present in small bowel disease, and observed in restricted cell lineages. This may impact on the epithelial immune response, cellular homeostasis and nutrient handling and influence appetite via increased satiety signalling in the gut-brain axis.
authors.affiliation: Inflammation Sciences Research Group and Manchester Academic Health Science Centre, University of Manchester, Manchester, M13 9PL, UK. gwmoran@ucalgary.ca
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Moran
authors.forename: Joanne
authors.initials: J
authors.lastname: Pennock
authors.forename: John T
authors.initials: JT
authors.lastname: McLaughlin
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D053379:Chromogranin A / Q000235:genetics / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019858:Enteroendocrine Cells / Q000166:cytology* / Q000378:metabolism*; D015870:Gene Expression; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019894:Peptide YY / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053379:Chromogranin A; D018398:Homeodomain Proteins; C109220:NBPhox protein; D012333:RNA, Messenger; D014157:Transcription Factors; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; C486451:UBE4A protein, human; D044767:Ubiquitin-Protein Ligases