Characterization of E. coli-specific T cells in Crohn's disease

克罗恩病中大肠杆菌特异性 T 细胞的表征

基本信息

项目摘要

PROJECT SUMMARY/ABSTRACT Several lines of evidence have implicated T cells in the pathogenesis of Crohn's disease, an uncontrolled inflammatory condition of the intestines in which immune cells overreact to the bacteria that live there. Previous studies of antigen-nonspecific T cells in Crohn's disease have not identified overall differences in them that would explain this over reactivity. However, we have recently identified CD4 T cells of the immune system that can react to a peptide from protein antigen (OmpC) made by one such bacteria (E. coli), to which antibodies are commonly seen only in people with Crohn's disease. We found that these OmpC-specific cells make IL-10 unless they come from Crohn's disease patients, and hypothesize that this defect plays a central role in the inflammation of Crohn's disease. IL-10 is a cytokine that clearly plays a central role in limiting inflammation in the intestines, because mice without the IL-10 gene and humans born with a mutation in the receptor for IL-10 both quickly develop severe enterocolitis, resembling Crohn's disease. The overall goal of the studies proposed here is to determine why these gut flora antigen-specific T cells fail to make IL-10 in Crohn's disease, as a mechanism by which tolerance to gut flora is lost in this condition. The novel approach is to integrate single cell gene expression and epigenetic analyses in these OmpC-specific T cells we can isolate with MHC-II tetramers. The hypothesis will be addressed in two Specific Aims with genome-wide expression differences correlated with IL-10 expression in Aim 1, and an epigenetic basis for failed IL-10 expression in Crohn's disease to be revealed in Aim 2. Together these studies will advance our understanding of abnormal IL-10 regulation by gut microbial antigen-specific T cells in Crohn's disease, and provide the foundation for determining how such a defect contributes to disease pathogenesis.
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James Daniel Lord其他文献

James Daniel Lord的其他文献

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{{ truncateString('James Daniel Lord', 18)}}的其他基金

Characterization of E. coli-specific T cells in Crohn's disease
克罗恩病中大肠杆菌特异性 T 细胞的表征
  • 批准号:
    10558631
  • 财政年份:
    2022
  • 资助金额:
    $ 25.95万
  • 项目类别:
Intestinal Dendritic Cell Modulation of Regulatory T Cell Function in IBD
IBD 中调节性 T 细胞功能的肠道树突状细胞调节
  • 批准号:
    8141666
  • 财政年份:
    2008
  • 资助金额:
    $ 25.95万
  • 项目类别:
Intestinal Dendritic Cell Modulation of Regulatory T Cell Function in IBD
IBD 中调节性 T 细胞功能的肠道树突状细胞调节
  • 批准号:
    7808332
  • 财政年份:
    2008
  • 资助金额:
    $ 25.95万
  • 项目类别:
Intestinal Dendritic Cell Modulation of Regulatory T Cell Function in IBD
IBD 中调节性 T 细胞功能的肠道树突状细胞调节
  • 批准号:
    7513622
  • 财政年份:
    2008
  • 资助金额:
    $ 25.95万
  • 项目类别:
Intestinal Dendritic Cell Modulation of Regulatory T Cell Function in IBD
IBD 中调节性 T 细胞功能的肠道树突状细胞调节
  • 批准号:
    8077443
  • 财政年份:
    2008
  • 资助金额:
    $ 25.95万
  • 项目类别:
Intestinal Dendritic Cell Modulation of Regulatory T Cell Function in IBD
IBD 中调节性 T 细胞功能的肠道树突状细胞调节
  • 批准号:
    8317680
  • 财政年份:
    2008
  • 资助金额:
    $ 25.95万
  • 项目类别:
Intestinal Dendritic Cell Modulation of Regulatory T Cell Function in IBD
IBD 中调节性 T 细胞功能的肠道树突状细胞调节
  • 批准号:
    7676870
  • 财政年份:
    2008
  • 资助金额:
    $ 25.95万
  • 项目类别:

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