Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells

抗原呈递细胞对脂肪组织炎症的调节

基本信息

  • 批准号:
    10391528
  • 负责人:
  • 金额:
    $ 49.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-01-11 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

Adipose tissue contains a network of leukocytes that respond to obesity by generating proinflammatory signals that contribute to metabolic disease. At the same time, there is strong evidence that many healthy immune responses are impaired in obesity and contribute to an increased severity of illness to many diseases that include respiratory viruses. We currently do not have a clear understanding of the mechanisms behind this dichotomy. Addressing this gap can reveal mechanisms by which a hyperactive immune system can be restrained to improve insulin resistance and can also identify mechanisms by which normal immune responses can be preserved to improve health in people with obesity. This proposal seeks to understand immune responses in adipose tissue by focusing on the mechanisms by which the innate and adaptive components of the adipose tissue immune system interact in mice and humans. Our central hypothesis is that the chronic pro-inflammatory environment generated by obesity triggers T cell and myeloid exhaustion. We further posit that the diversity of adipose tissue macrophages (ATM) and dendritic cells (ATDC) shape adipose tissue T cell responses that impair healthy resolution of adipose tissue inflammation. The premise for this hypothesis is based on the published work generated in the last grant cycle, as well as preliminary data demonstrating a impaired T cell activation capacity in obese adipose tissue from mice and humans associated with decrease diversity of T cells in obese humans and enrichment for novel subtypes of ATDC. Our approach will identify the mechanisms by which adipose tissue T cells become exhausted with dietary obesity by testing the hypothesis that the induction of T cell exhaustion profiles requires differential APC signals and the induction of BTLA receptors in T cells. We will also evaluate the hypothesis that endogenous glucocorticoids alter the ability of ATMs and ATDC to activate T cells in a way that promotes exhaustion. Completing these aims further advance the understanding of the cell-cell communication networks that are generated in adipose tissue and how they contribute to metabolic disease.
脂肪组织包含一个白细胞网络,通过产生促炎信号对肥胖做出反应,促炎信号导致代谢疾病。与此同时,有强有力的证据表明,许多健康的免疫反应在肥胖中受损,并导致包括呼吸道病毒在内的许多疾病的严重程度增加。我们目前对这种二分法背后的机制没有明确的认识。解决这一差距可以揭示过度活跃的免疫系统可以被抑制以改善胰岛素抵抗的机制,也可以确定可以保留正常免疫反应以改善肥胖患者健康的机制。该提案旨在通过关注脂肪组织免疫系统的先天和适应性成分在小鼠和人类中相互作用的机制来了解脂肪组织中的免疫反应。我们的中心假设是肥胖产生的慢性促炎环境触发T细胞和骨髓衰竭。我们进一步证实,脂肪组织巨噬细胞(ATM)和树突状细胞(ATDC)的多样性形成脂肪组织T细胞反应,损害脂肪组织炎症的健康解决。这一假设的前提是基于上一个资助周期中产生的已发表的工作,以及初步数据,这些数据表明小鼠和人类肥胖脂肪组织中T细胞活化能力受损,与肥胖人类T细胞多样性降低和ATDC新型亚型富集相关。我们的方法将确定脂肪组织T细胞成为耗尽与饮食性肥胖的机制,通过测试的假设,T细胞耗竭配置文件的诱导需要差异APC信号和T细胞中BTLA受体的诱导。我们还将评估内源性糖皮质激素改变ATM和ATDC以促进疲劳的方式激活T细胞的能力的假设。完成这些目标进一步推进了对脂肪组织中产生的细胞-细胞通信网络以及它们如何导致代谢疾病的理解。

项目成果

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Carey N Lumeng其他文献

Carey N Lumeng的其他文献

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{{ truncateString('Carey N Lumeng', 18)}}的其他基金

Depot-specific regulation of metabolism by adipose tissue stromal cell subpopulations
脂肪组织基质细胞亚群对代谢的特异性调节
  • 批准号:
    10685079
  • 财政年份:
    2022
  • 资助金额:
    $ 49.93万
  • 项目类别:
Adipose Tissue Macrophage Control of Metabolic Dysfunction in Diabetes
脂肪组织巨噬细胞对糖尿病代谢功能障碍的控制
  • 批准号:
    9400748
  • 财政年份:
    2017
  • 资助金额:
    $ 49.93万
  • 项目类别:
The Impact of Postnatal Overnutrition on the Adipose Tissue Immune System and Metabolic Inflammation
产后营养过剩对脂肪组织免疫系统和代谢炎症的影响
  • 批准号:
    9023650
  • 财政年份:
    2015
  • 资助金额:
    $ 49.93万
  • 项目类别:
Regulation of Adipose Tissue Inflammation by Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
  • 批准号:
    8021103
  • 财政年份:
    2011
  • 资助金额:
    $ 49.93万
  • 项目类别:
Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
  • 批准号:
    9113707
  • 财政年份:
    2011
  • 资助金额:
    $ 49.93万
  • 项目类别:
Regulation of Adipose Tissue Inflammation by Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
  • 批准号:
    8409818
  • 财政年份:
    2011
  • 资助金额:
    $ 49.93万
  • 项目类别:
Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
  • 批准号:
    10579916
  • 财政年份:
    2011
  • 资助金额:
    $ 49.93万
  • 项目类别:
Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
  • 批准号:
    9234511
  • 财政年份:
    2011
  • 资助金额:
    $ 49.93万
  • 项目类别:
Regulation of Adipose Tissue Inflammation By Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
  • 批准号:
    10229169
  • 财政年份:
    2011
  • 资助金额:
    $ 49.93万
  • 项目类别:
Regulation of Adipose Tissue Inflammation by Antigen Presenting Cells
抗原呈递细胞对脂肪组织炎症的调节
  • 批准号:
    8212056
  • 财政年份:
    2011
  • 资助金额:
    $ 49.93万
  • 项目类别:

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