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P066. IL-17A has dual actions in the induction of colitis

C.S. Eun, D.S. Han, A.R. Lee, H.-J. Park, Hanyang University Guri Hospital, Gastroenterology, Guri, Korea, Republic of

Background

Th17/IL-23 pathway has been linked to the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease. However, the function of IL-17A in inflammatory bowel disease remains unclear. We investigated the role of IL-17A on the intestinal inflammation using dextran sodium sulfate (DSS) and trinitrobenzene sulfonic acid (TNBS) induced colitis model and T-cell transfer induced mouse colitis model.

Methods

Acute colitis was induced in IL-17A−/− and C57BL/6 wild-type (WT) mice by administering 2.7% DSS orally in drinking water for five days or by introducing 3.2 mg of TNBS in 50% ethanol into the rectum. In the T-cell transfer induced colitis model, purified CD4+ CD45RBhigh T cells (1*106) from IL-17A−/− or WT mice were injected intraperitoneally into Rag2−/− recipients. Clinical activities including weight loss and histologic findings of colonic segments were examined. Proinflammatory cytokine levels were measured by ELISA in the supernatants of colonic tissue explants.

Results

After DSS or TNBS treatment, significant weight loss was developed both in IL-17A−/− and WT mice compared to mice not treated with DSS or TNBS. Clinical and histological activities of colitis, and pro-inflammatory cytokine levels in colonic tissue explants were attenuated in chemical-treated IL-17A−/− mice compared to chemical-treated WT mice. On the contrary, there were no significant differences in weight loss, histological scores, and proinflammatory cytokine levels between recipients of IL-17A−/− CD45RBhigh T cells and recipients of WT CD45RBhigh T cells, although CD45RBhigh T cells from both donor mice induced significant colitis in the Rag2−/− recipients.

Conclusion

In chemically induced colitis models, IL-17A appear to be pathogenic, whereas in the T-cell transfer induced mouse colitis model, IL-17A may be dispensable for colitis induction.