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* = Presenting author

P022. IL-23 responsive innate lymphoid cells are increased in inflammatory bowel disease

A. Geremia1, C.V. Arancibia1, M.P.P. Fleming2, B. Singh2, S. Travis1, F. Powrie1

1Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom; 2Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, United Kingdom

Aim: A pivotal role for IL-23 in colitis has emerged from human and murine studies. Inflammatory bowel disease (IBD) is associated with polymorphisms in the IL-23R gene and Th17 cytokines are increased in the colon and serum of patients. IL-23 driven inflammation has been primarily linked to the activity of T helper (Th)-17 cells, however we have recently identified a novel population of murine innate lymphoid cells (ILC) that produce IL-17, IL-22 and IFN-γ in response to IL-23 and mediate innate colitis. Aim of this study was to evaluate the role of IL-23 driven ILC in human chronic intestinal inflammation in patients with IBD.

Material and Methods: We isolated lamina propria mononuclear cells (LPMC) from IBD patients and colorectal cancer patients as non-inflammatory controls. CD3− cells and CD56− and CD56+ ILC subsets were sorted by FACS. Expression of Th-17 signature genes was measured by qPCR ex vivo and after in vitro stimulation with IL-23. Frequency of CD127+CD56+ and CD127+CD56− ILC subsets and intracellular expression of IL-17 and IFN-γ was assessed by FACS in LPMC from patients and controls.

Results: Our results show increased expression of the Th-17 associated cytokine genes IL-17A and IL-17F but not IL-22 and IL-26 amongst intestinal CD3− cells in IBD. Analysis of CD56− and CD56+ ILC subsets showed that IL-17A and IL-17F expression is restricted to CD56− cells, while IL-23 induces IL-22 and IL-26 in the CD56+ compartment. Furthermore, we observed a marked selective increase in the CD127+CD56− lymphoid tissue inducer (LTi)-like cells in the inflamed colon and ileum of patients with Crohn's disease, but not in the inflamed colon of patients with ulcerative colitis.

Conclusions: These results indicate that IL-23 responsive ILC are present in the human intestine and that intestinal inflammation in Crohn's disease is associated with the selective accumulation of a phenotypically distinct LTi-like population characterized by inflammatory cytokine expression. ILC may contribute to intestinal inflammation through cytokine production and inflammatory cell recruitment and represent a novel tissue-specific target for the treatment of IBD.