title: Innate immune factors in the development and maintenance of pouchitis.
abstract: BACKGROUND
  Tight junction proteins (TJPs) and dendritic cells (DC) are critical in the pathogenesis of inflammatory bowel diseases. The ileal pouch formed by restorative proctocolectomy provides a unique human model for studying the pathogenesis of inflammatory bowel diseases. Data implicate the microbiota in the pathogenesis of pouchitis, while the role of innate immune factors remains unclear. We performed longitudinal and cross-sectional studies of patients after restorative proctocolectomy and assessed TJP and DC characteristics in the ileal pouch.
  
  
  METHODS
  Mucosal biopsies were taken from the ileal pouch of patients with ulcerative colitis (UC) and familial adenomatous polyposis (n = 8). Of patients with UC, one group (n = 5) was followed longitudinally over the first year after ileostomy closure, another group had pouchitis (n = 15), and another group no inflammation (n = 18). Dendritic cell phenotype and epithelial cell TJP expression were assessed using flow cytometric analysis.
  
  
  RESULTS
  Increased epithelial expression of the "pore-forming" TJP claudin 2, and DC expression of gut-homing markers CCR 9 and integrin β7, occurred early after ileostomy closure. In patients with UC with pouchitis, epithelial expression of ZO-1 and claudin 1 were reduced, DC were activated with increased CD40, and Toll-like receptor 4 expression increased. In pouchitis, DC expressing CCR 9 were decreased, whereas DC expressing β7 increased.
  
  
  CONCLUSIONS
  Abnormalities were found in TJP expression in the pouch of patients with UC, in particular, increased expression of the pore-forming claudin 2 as an early event in the development of pouch inflammation and an aberrant DC phenotype was characterized in the ileal pouch of patients with UC.
authors.affiliation: *Department of Gastroenterology, St Mark's Hospital, London, United Kingdom; †Antigen Presentation Research Group, Imperial College London, Northwick Park and St Mark's Campus, London, United Kingdom; ‡Department of Gastroenterology, The Rayne Institute, St Thomas' Hospital, London, United Kingdom; and §Department of Surgery, St Mark's Hospital, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Landy
authors.forename: Hafid O
authors.initials: HO
authors.lastname: Al-Hassi
authors.forename: Emma
authors.initials: E
authors.lastname: Ronde
authors.forename: Nick R
authors.initials: NR
authors.lastname: English
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Mann
authors.forename: David
authors.initials: D
authors.lastname: Bernardo
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Ciclitira
authors.forename: Susan K
authors.initials: SK
authors.lastname: Clark
authors.forename: Stella C
authors.initials: SC
authors.lastname: Knight
authors.forename: Ailsa L
authors.initials: AL
authors.lastname: Hart
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000150:complications* / Q000378:metabolism / Q000601:surgery; D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000150:complications* / Q000378:metabolism / Q000601:surgery; D039021:Colonic Pouches / Q000473:pathology*; D003430:Cross-Sectional Studies; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007081:Ileostomy; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019449:Pouchitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016737:Proctocolectomy, Restorative; D011379:Prognosis; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D007155:Immunologic Factors