Initiation of Experimental Colitis by Commensal Flora

描述(由申请人提供)：如PA-O 1-132所述，“具有医学培训和研究经验的临床医生-科学家迫切需要研究人类环境相关疾病的问题。暴露于环境中的生物衍生毒素与临床结果之间的联系一直是一个持续的挑战。”炎症性肠病(IBD)是一种病因不明的慢性复发性疾病。调节炎症或引发新一轮症状的环境事件完全没有特征。在健康的个体中，暴露于肠道生物病原体会导致高度调节的免疫反应，首先清除有机体，然后恢复到受控状态。我们的前提是，在IBD中观察到的慢性炎症是由于黏膜免疫反应无法恢复到这种受控状态所致。因此，我们提出了以下中心假设：实验性IBD小鼠模型的炎症是由粘膜T细胞对肠道细菌抗原的反应引发的。我们的目的是研究肠道微生物环境与宿主黏膜免疫系统的相互作用，以及它们在IBD的诱导、持续和缓解中各自的作用。

DESCRIPTION (provided by applicant): As stated in PA-O 1-132, "there is a critical need for clinician-scientists with the medical training and research experience to investigate problems of environmentally relevant disease in humans. The linking of exposures to biologically derived toxins in the environment to clinical outcomes has been a consistent challenge." Inflammatory bowel disease (IBD) is a chronic and relapsing disease of unknown etiology. The environmental events that modulate inflammation or trigger a new round of symptoms are completely uncharacterized. In a healthy individual exposure to an intestinal biological pathogen results in a highly regulated immune response that first clears the organism and then returns to a controlled state. it is our premise that the chronic inflammation observed in IBD results from an inability of the mucosal immune response to return to this controlled state. Thus we present the following central hypothesis: Inflammation in experimental murine models of IBD is initiated by mucosal T cell responses to enterobacterial antigens. Our aim is to investigate the interaction of the microbiological environment of the gut with the host mucosal immune system, and their respective contributions to induction, perpetuation, and remission of IBD.