T1718 Natural Killer Cell Responses in Both Acute and Chronic Phases of a Murine Model of Experimental Colitis

Introduction/aim: Natural killer (NK) cells contribute to host resistance against viruses, bacteria and certain parasites as well as providing immune surveillance against the development of tumours. Recently NK cells have been implicated in the modulation of various autoimmune diseases. In this study we have investigated the recruitment and functional characteristics of NK cells in an experimental model of colitis. Methods: Female C57BL/6 mice were exposed to 6 days of dextran sulphate sodium (DSS) followed by 20 days of water. Organs (spleens, mesenteric lymph nodes and colons)were harvested during both acute and chronic phases of colitis to determine percentage, distribution, activation status and cytokine/cytotoxic profiles. Results: We observed that as early as 1 day post DSS, animals were found to have significant increases in both the percentage and activation status of NK cells in comparison to controls, which continued throughout the study. With regards to their cytotoxic/cytokine profile we observed significant increases of perforin+ NK cells initially (D1), followed by increases in granzyme B producing NK cells.We also observed a diverse range of cytokine being produced from NK cells during colitis, including both anti-inflammatory (IL-4 and IL-10) and pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6 and IL-17). Conclusions: Collectively, our data suggest that NK cells might play a prominent role in the establishment of immune responses in DSS-induced colitis and therefore may have a consequent impact on the pathogenesis of inflammatory bowel disease (IBD).