Initiation of Experimental Colitis by Commensal Flora

描述（由申请人提供）：如PA-O - 1-132所述，“迫切需要具有医学培训和研究经验的临床科学家来调查人类环境相关疾病的问题。将暴露于环境中生物来源的毒素与临床结果联系起来一直是一个挑战。”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是完全没有特征的。在健康个体中，暴露于肠道生物病原体会导致高度调节的免疫反应，首先清除生物体，然后返回到受控状态。我们的前提是，在IBD中观察到的慢性炎症是由于粘膜免疫反应无法恢复到这种受控状态。因此，我们提出以下中心假设：IBD实验小鼠模型中的炎症是由粘膜T细胞对肠杆菌抗原的反应引起的。我们的目的是研究肠道微生物环境与宿主粘膜免疫系统的相互作用，以及它们各自在IBD的诱导、延续和缓解中的作用。

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.