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The Role of Toll-like Receptor 4 Positive T Cells in Intestinal Immune Regulation

The Role of Toll-like Receptor 4 Positive T Cells in Intestinal Immune Regulation
Toll样受体4阳性T细胞在肠道免疫调节中的作用
批准号:
8484392
负责人:
Mirac Nedim Ince
金额:
$14.75万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-07-15 至 2014-06-30

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中文摘要
翻译
本申请提出研究Toll样受体4阳性(TLR 4)T细胞在调节T细胞增殖中的作用。 炎症性肠病小鼠模型。TLR 4 + T淋巴细胞在免疫调节过程中出现 肠道蠕虫感染。它们识别细菌脂多糖(LPS)并产生免疫反应。 调节性TGF-β,而不是促炎细胞因子。我们假设 LPS刺激的粘膜T细胞TGF-β分泌对于肠道免疫调节是重要的。我们提出 来验证我们的假设未发炎野生型或结肠炎动物和小鼠中的多脑回感染模型 参与TLR 4信号通路的蛋白质遗传缺陷,如MyD 88-/-或TRIF-/-小鼠 菌株在某些实验中,我们计划使用药理学试剂或互补的短抑制剂。 RNA(sIRNA)抑制TLR 4信号通路的某些元件。具体目标#1:我们将 确定LPS刺激后TLR 4+肠T细胞的表型和功能变化。具体 目标#2:我们将定义肠道TLR 4 + T细胞中导致TGF-β产生的信号元件。 具体目标#3:我们将确定TLR 4 + T细胞在诱导或维持肠道免疫应答中的作用。 小鼠结肠炎模型中的免疫平衡。这一建议可能会导致新的细胞识别 在IBD的控制中起重要作用的蛋白质。通过药理学试剂靶向这些分子可能导致 炎症性肠病的有效和更安全的医疗管理。 该提案的长期目标是将主要研究者提升为独立医生 胃肠病学和粘膜免疫学科学家,在细胞和分子方面具有重要背景 生物学申请人于2007年在爱荷华州大学完成了胃肠病学研究, 在他被任命为终身助理教授的第一年。这项研究将在 爱荷华州大学,由大卫埃利奥特、保罗罗斯曼和加里亨宁哈克博士指导。在 此外,一个由教员组成的咨询委员会将提供职业发展建议。该奖项 将使首席研究员掌握细胞和分子生物学的研究技能。
英文摘要
This application proposes to investigate the role of toll-like receptor 4 positive (TLR4) T cells in regulating inflammatory bowel disease in mouse models. TLR4+ T lymphocytes emerge during immune modulatory helminth infection in the intestine. They recognize bacterial lipopolysaccharide (LPS) and produce immune regulatory TGF-beta but not proinflammatory cytokines, when stimulated with LPS. We hypothesize that LPS-stimulated mucosal T cell TGF-beta secretion is important for intestinal immune regulation. We propose to test our hypothesis in H. polygyrus infection model in uninflamed wild-type or colitic animals and in mice genetically deficient for proteins that participate in TLR4 signaling pathway, like MyD88-/- or TRIF-/- mouse strains. In certain experiments we plan to employ pharmacologic agents or complementary short inhibitory RNA (sIRNA) contructs to inhibit certain elements of TLR4 signaling pathway. Specific Aim #1: We will determine phenotypic and functional changes in TLR4+ intestinal T cells following LPS stimulation. Specific Aim #2: We will define the signaling elements in intestinal TLR4+ T cells that lead to TGF-beta production. Specific Aim #3: We will identify the role of TLR4+ T cells in the induction or maintenance of intestinal immune balance in mouse models of colitis. This proposal may lead to the identification of novel cellular proteins important in the control of IBD. Targeting these molecules by pharmacologic agents may lead to potent and safer medical management of inflammatory bowel disease. The long-term objective of this proposal is to advance the principal investigator to an independent physician scientist in gastroenterology and mucosal immunology with significant background in cellular and molecular biology. The applicant has completed fellowship in gastroenterology at the University of Iowa in 2007 and is in his first year of appointment as an assistant professor on tenure track. The research will take place at the University of Iowa under the mentorship of Drs. David Elliott, Paul Rothman and Gary Hunninghake. In addition, an advisory committee of faculty members will provide career development advice. The award would allow the principal investigator to master research skills in cellular and molecular biology.
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Regulation of graft versus host disease with in vivo generated regulatory T cells
  • 批准号:
    9240776
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2017
  • 负责人:
    Mirac Nedim Ince
  • 依托单位:
Mixed Chimerism-Dependent Tolerance After Myeloablative Bone Marrow Transplantation
  • 批准号:
    10449110
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2017
  • 负责人:
    Mirac Nedim Ince
  • 依托单位:
Mixed Chimerism-Dependent Tolerance After Myeloablative Bone Marrow Transplantation
  • 批准号:
    10259947
  • 项目类别:
  • 资助金额:
    $0.0万
  • 财政年份:
    2017
  • 负责人:
    Mirac Nedim Ince
  • 依托单位:
The Role of Toll-like Receptor 4 Positive T Cells in Intestinal Immune Regulation
  • 批准号:
    8082745
  • 项目类别:
  • 资助金额:
    $14.75万
  • 财政年份:
    2009
  • 负责人:
    Mirac Nedim Ince
  • 依托单位:
海外基金