Induction and activation of adaptive immune populations during acute and chronic phases of a murine model of experimental colitis.

摘要

BACKGROUND: Dextran sodium sulphate (DSS) is commonly used to induce intestinal inflammation in rodents. Despite its continuing importance as a model system for examining IBD pathogenesis, the mucosal and systemic immune responses have not been comprehensively documented. AIMS: The purpose of this study was to dissect functional and phenotypic changes in both immune compartments associated with acute and chronic DSS-induced colitis. METHODS: C57BL/6 mice were exposed to 3% DSS for 6 days followed by 20 days of water, and organs (spleens, MLN and colons) were harvested during both acute and chronic phases of colitis to examine innate and adaptive cell populations. RESULTS: As early as 1 day post DSS, significant changes in the percentage, distribution and activation status of all innate cell populations examined were noted. These striking differences continued in systemic and mucosal lymphoid tissues throughout the acute phase (days 5-12). Significantly, during the late acute and chronic phases T and B cells accumulated in the colon. In contrast, in the spleens of chronically inflamed mice T and B cells were significantly decreased whereas neutrophils, macrophages, and IL-6 and IL-17 positive cells were increased. CONCLUSIONS: Our data provides important insights into the mucosal and systemic immune responses induced by DSS administration. Notably, we show that adaptive immune responses are induced during both acute and chronic colitis. This will facilitate a more informed and sophisticated use of this model both for investigating basic mechanisms of intestinal inflammation and for the evaluation of potential new therapeutic agents for IBD.