The role of IL-10 in stabilizing natural regulatory T cells

IL-10 在稳定天然调节性 T 细胞中的作用

基本信息

  • 批准号:
    8377919
  • 负责人:
  • 金额:
    $ 46.62万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-07-01 至 2015-06-30
  • 项目状态:
    已结题

项目摘要

Natural regulatory T cells (nTreg) differentiate to acquire FoxpS expression and suppressive function in the thymus. These cells have been thought of as a highly stable lineage, but recent work suggests that they may lose Foxp3 expression and acquire various effector functions, particularly under conditions of lymphopenia and/or inflammation. It will be important to understand the conditions under which this loss may occur, if the expansion and transfer of nTreg, or in vivo augmentation of nTreg activity, will ever be used as immune therapies. We have made the surprising observation that nTreg transferred to Rag-/- mice require exogenous IL-10 from CD11b+ intestinal myeloid cells in order to prevent colitis. The lapsed nTreg in IL-10 deficient recipients acquire a distinct THI-like cytokine secretion pattern, characterized by the secretion of IFNy, but not TNF or IL-17. The experiments in this application therefore will use genetic technologies, cellular immunology methods and in vivo disease models to better understand the molecular changes and cellular interactions that underlie the striking in vivo changes in nTreg that we have observed. We will determine if the loss of nTreg function is reversible (Aim 1), and in Aim 2 we will fully characterize the function ofthe lapsed cells, and will determine if nTreg acting in other sites also require IL-10 from cells other than lymphocytes. Additionally, in this Aim we will examine the status ofthe Foxp3 locus in lapsed Treg, and the overall pattern of epigenetic modifications in their chromatin. We will determine in Aim 3 if induced Treg (ITreg) display a similar requirement for paracrine IL-10, and if the use of more effective induction methods, such as retinoic acid or alterations induced by viral infection, can fortify iTreg so they can function without exogenous IL-10. In aim 4, we will compare CD11b+ intestinal myeloid celis from different parts ofthe mucosal immune system for their ability to stimulate the generation of ITreg and the stabilization of nTreg. In summary, the proposed experiments build on our novel preliminary findings in order to achieve a deep understanding of the pathway leading to the dangerous loss of suppressive function in nTreg, and the means by which this can be reversed or prevented.
自然调节性T细胞(nTreg)分化获得FoxpS的表达和抑制功能

项目成果

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MITCHELL KRONENBERG其他文献

MITCHELL KRONENBERG的其他文献

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{{ truncateString('MITCHELL KRONENBERG', 18)}}的其他基金

Host nutrients permit immune evasion of NKT cell anti-bacterial responses
宿主营养物质允许免疫逃避 NKT 细胞抗菌反应
  • 批准号:
    10312774
  • 财政年份:
    2018
  • 资助金额:
    $ 46.62万
  • 项目类别:
Host nutrients permit immune evasion of NKT cell anti-bacterial responses
宿主营养物质允许免疫逃避 NKT 细胞抗菌反应
  • 批准号:
    10089228
  • 财政年份:
    2018
  • 资助金额:
    $ 46.62万
  • 项目类别:
HVEM: A TNF family receptor that influences mucosal immunity and the microbiome
HVEM:影响粘膜免疫和微生物组的 TNF 家族受体
  • 批准号:
    9294945
  • 财政年份:
    2016
  • 资助金额:
    $ 46.62万
  • 项目类别:
The role of natural killer T cells in the innate response to lung infection
自然杀伤 T 细胞在肺部感染先天反应中的作用
  • 批准号:
    8632820
  • 财政年份:
    2014
  • 资助金额:
    $ 46.62万
  • 项目类别:
Research Resources: Epigenomic and Transcriptomic Profiles of Human Immune Cells
研究资源:人类免疫细胞的表观基因组和转录组图谱
  • 批准号:
    9112842
  • 财政年份:
    2014
  • 资助金额:
    $ 46.62万
  • 项目类别:
Research Resources: Epigenomic and Transcriptomic Profiles of Human Immune Cells
研究资源:人类免疫细胞的表观基因组和转录组图谱
  • 批准号:
    8895831
  • 财政年份:
    2014
  • 资助金额:
    $ 46.62万
  • 项目类别:
Research Resources: Epigenomic and Transcriptomic Profiles of Human Immune Cells
研究资源:人类免疫细胞的表观基因组和转录组图谱
  • 批准号:
    8740928
  • 财政年份:
    2014
  • 资助金额:
    $ 46.62万
  • 项目类别:
The role of natural killer T cells in the innate response to lung infection
自然杀伤 T 细胞在肺部感染先天反应中的作用
  • 批准号:
    8862370
  • 财政年份:
    2014
  • 资助金额:
    $ 46.62万
  • 项目类别:
The role of IL-10 in stabilizing natural regulatory T cells
IL-10 在稳定天然调节性 T 细胞中的作用
  • 批准号:
    8495226
  • 财政年份:
    2013
  • 资助金额:
    $ 46.62万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    8495232
  • 财政年份:
    2013
  • 资助金额:
    $ 46.62万
  • 项目类别:
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