Initiation of Experimental Colitis by Commensal Flora

共生菌群引发实验性结肠炎

• 批准号: 6793151
• 负责人: MICHELE R ETLING
• 金额: $ 3.46万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6793151
• 关键词: Enterobacteriaceae; T lymphocyte; bacteria infection mechanism; biotherapeutic agent; chronic disease /disorder; colitis; enteric bacteria; enzyme linked immunosorbent assay; flow cytometry; gene environment interaction; genetically modified animals; immunocytochemistry; in situ hybridization; inflammation; inflammatory bowel diseases; laboratory mouse; mucosal immunity; polymerase chain reaction; predoctoral investigator; western blottings

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.

描述（由申请人提供）：如 PA-O 1-132 中所述，“迫切需要接受过医学培训和研究经验的临床医生科学家来调查人类环境相关疾病的问题。环境中的衍生毒素对临床结果的影响一直是一个挑战。”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完全没有特征。在健康个体中，接触肠道生物病原体会导致高度调节的免疫反应，首先清除微生物，然后恢复到受控状态。我们的前提是，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造成的。因此，我们提出以下中心假设：IBD 实验鼠模型中的炎症是由粘膜 T 细胞对肠杆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粘膜免疫系统的相互作用，以及它们各自对 IBD 的诱导、持续和缓解的贡献。