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Innate immune factors in the development and maintenance of pouchitis.
- Source :
-
Inflammatory bowel diseases [Inflamm Bowel Dis] 2014 Nov; Vol. 20 (11), pp. 1942-9. - Publication Year :
- 2014
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Adenomatous Polyposis Coli metabolism
Adenomatous Polyposis Coli surgery
Adult
Aged
Colitis, Ulcerative metabolism
Colitis, Ulcerative surgery
Cross-Sectional Studies
Dendritic Cells metabolism
Female
Follow-Up Studies
Humans
Ileostomy
Immunity, Innate
Longitudinal Studies
Male
Middle Aged
Pouchitis metabolism
Pouchitis pathology
Proctocolectomy, Restorative
Prognosis
Tight Junctions metabolism
Tight Junctions pathology
Young Adult
Adenomatous Polyposis Coli complications
Colitis, Ulcerative complications
Colonic Pouches pathology
Dendritic Cells pathology
Immunologic Factors metabolism
Pouchitis etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1536-4844
- Volume :
- 20
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Inflammatory bowel diseases
- Publication Type :
- Academic Journal
- Accession number :
- 25222658
- Full Text :
- https://doi.org/10.1097/MIB.0000000000000182