P010. Upregulation of gut homing markers on dendritic cells in the functioning and inflamed ileo-anal pouch
J. Landy1, H.O. Al-Hassi2, E. Ronde2, S. Peake1, N. English2, E. Mann2, D. Bernardo2, C.T. Tee2, R.J. Nicholls3, P.J. Ciclitira4, S.K. Clark5, S. Knight2, A.L. Hart1
1St Mark's Hospital, IBD Unit, London, United Kingdom; 2Antigen Presentation Research Group, Imperial College, London, United Kingdom; 3Imperial College, Department of Biosurgery and Surgical Technology, London, United Kingdom; 4St Thomas' Hospital, Gastroenterology, London, United Kingdom; 5St Mark's Hospital, Colorectal Surgery, London, United Kingdom
Background: Dendritic cells (DC) regulate intestinal immune responses to the gut microbiota and imprint gut homing properties on lymphocytes, a critical step in the development of intestinal inflammation . The pouch microbiota alters following ileostomy closure toward a colon-like community . We hypothesize that alteration of the pouch microbiota following ileostomy closure may modulate the expression of homing markers on DC. We performed a longitudinal study assessing the expression of intestinal homing markers on lamina propria DC from UC patients in the first 6 months post-ileostomy closure and in patients with chronic pouchitis.
Methods: Mucosal biopsy samples were taken from UC patients undergoing restorative proctocolectomy (RPC), from the ileostomy afferent loop, pouch pre-ileostomy closure (P0), the pouch 6 months post-ileostomy closure (in the same patients), and other UC RPC patients with chronic pouchitis. Lamina propria DC were isolated from biopsy tissue by collagenase digestion and were identified as an HLA DR+, lineage- (CD3‑, CD14‑, CD16‑, CD19‑, CD34‑, CD56‑) population. The homing markers β7 and CCR 9 expression on DC were measured by flow cytometry. T‑tests were performed for statistical analysis.
Results: The proportion of DC expressing β7 was increased 6 months post ileostomy closure compared to ileostomy and P0 (p = 0.038). In chronic pouchitis patients, β7 expression was elevated compared with ileostomy (p = 0.005), P0 (p = 0.003) and 6 month pouch samples (ns). DC CCR9 expression was significantly greater in ileostomy (p = 0.015) and in pouch 6 months after ileostomy closure (p = 0.049), compared with P0 (Table 1).
|UC ileostomy (n = 9)||6.4% ±3.2||42.3% ±5.3|
(Ileostomy v P0; p = 0.015)
|Pre-ileostomy closure pouch (P0) (n = 9)||5.7% ±1.8|
(P0 v P 6 months; p = 0.038)
(P0 v P 6 months; p = 0.049)
|6 month pouch (n = 5)||17.8% ±3.1||47.2% ±1.9|
|Pouchitis (n = 6)||37.5% ±10.2|
(Pouchitis v P0; p = 0.003)
Conclusions: DC expression of gut homing markers increased following ileostomy closure. In chronic pouchitis gut homing markers appear elevated, but reflect a more colonic homing profile. Increased expression of gut homing markers on DC in UC RPC patients is likely to be a critical step in the development of pouch inflammation.
1. Hart AL et al. (2010), Homing of immune cells: role in homeostasis and intestinal inflammation. IBD, 196977, 16.
2. Kohyama A et al. (2009), Bacterial population moves toward a colon-like community in the pouch after total proctocolectomy, Surgery, 43547, 145.