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P007. The aetiology, immune activation and homing profile of dendritic cells in fistulating perianal Crohn's disease

N.A. Yassin1, H. Al-Hassi2, G.H. Lee2, G. Malietzis2, P. Tozer3, D. Bernardo-Ordiz2, E. Mann2, R.K.S. Phillips1, S. Knight2, A.L. Hart4, 1St Mark's Hospital and Academic Institute, Harrow, The Department of Colorectal Surgery, London, 2Antigen Presentation Research Group, St Mark's and Northwick Park Hospitals, 3St Mark's Hospital and Academic Institute, Harrow, London, 4IBD Unit, St Mark's Hospital and Academic Institute, Harrow, London, United Kingdom

Background

Genetic, microbiological and immunological factors play a role in the aetiology of Crohn's disease (CD). The aetiology of fistulating perianal Crohn's disease remains unclear and the disease a challenge to treat.

Dendritic cells (DC) are antigen presenting cells that stimulate and regulate immune responses. Tissue DC have tissue-specific markers and imprint homing markers on T cells directing them to specific organs such as gut (β 7 integrin) and skin (cutaneous lymphocyte-associated antigen CLA). DC recognise microbial ligands via Toll-Like receptors (TLR) to modulate the immune response. We aimed to characterise the activation status and homing profile of DC of Crohn's and idiopathic perianal fistulae.

Methods

Biopsy samples were taken from anal fistula tracts of 14 Crohn's and 14 idiopathic patients. Samples were incubated in medium overnight and ‘walk-out’ cells were recovered from the supernatant and analysed by flow cytometry. DC were identified as HLA-DR positive and lineage (CD3, CD14, CD16, CD19, CD34 and CD56) negative. The expression of CLA, β 7, TLR 2 and 4 was determined. Unpaired student t test was used for comparisons and p < 0.05 was considered as significant.

Results

The percentage of DC with the gut homing marker β 7 was significantly higher in patients with Crohn's (p < 0.01) compared with idiopathic perianal fistulae (p < 0.01). However, there was no significant difference in expression of CLA. When comparing β 7 and CLA expression within the Crohn's group, the percentage of DC expressing β 7 was significantly higher than CLA (p < 0.0001); within the idiopathic group there was no significant difference between β 7 and CLA expression.

There was no significant difference between Crohn's and idiopathic fistulae with regards to the percentage of DC expressing TLR2 or TLR4. However, in Crohn's perianal fistulae, fewer cells expressed TLR2 than TLR4 (p < 0.008).

Conclusion

Increased expression of the gut homing marker β 7 on dendritic cells of Crohn's perianal fistulae suggests the importance of β 7 in this disease and may provide a therapeutic target.