Role of glutamine metabolism in Dendritic Cell Development

谷氨酰胺代谢在树突状细胞发育中的作用

基本信息

  • 批准号:
    10735230
  • 负责人:
  • 金额:
    $ 32.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-01 至 2026-08-31
  • 项目状态:
    未结题

项目摘要

Project Summary Conventional dendritic cells (CDC) play a central role in protective immunity by connecting innate and adaptive immune responses. CDCs can distinguish `self' from `non-self' (example pathogen) or `altered-self' (example cancer) through specialized pattern recognition receptors and help orchestrate the appropriate adaptive immune response. CDC1 and CDC2 are the two major subsets of CDCs with CDC1s having the unique capacity to cross- present antigens that is critical for immunity against viruses and cancer. Circulating precursors of CDCs (Pre- CDCs) infiltrate tissue where they differentiate into CDC1 and CDC2. The relative distribution of these CDC subsets differ between tissue types and under pathological conditions, suggesting a role of tissue microenvironment in Pre-CDC differentiation. What factors in the tissue microenvironment might regulate this process, however, remains poorly understood. Our preliminary studies show that CDC1 differentiation is regulated by local availability of the amino acid glutamine through its metabolic conversion into glutamate. Glutamine uptake and utilization increases significantly in rapidly proliferating cells or during catabolic stress, potentially creating a glutamine deficient local microenvironment. Hence, we hypothesize that metabolic adaptations in tissue alters local CDC1 differentiation by modulating glutamine levels. In this proposal, we seek to understand which steps of CDC1 differentiation is regulated by glutamate and its underlying molecular mechanism. We will focus on epigenetic regulation of gene expression and oxidative stress as potential pathways by which glutamate mediates this effect. Findings from the proposed work can potentially open new lines of research linking tissue metabolic adaptations to its immune microenvironment.
项目摘要 传统的树突状细胞(CDC)通过连接先天性和适应性在保护性免疫中发挥核心作用 免疫反应。CDC可以区分“自我”与“非自我”(例如病原体)或“改变的自我”(例如 癌症)通过专门的模式识别受体,并帮助协调适当的适应性免疫 反应CDC 1和CDC 2是CDC的两个主要亚类,其中CDC 1具有独特的跨膜能力, 这些抗原对于抵抗病毒和癌症的免疫至关重要。CDCs的循环前体(前 CDC)浸润组织,在那里它们分化成CDC 1和CDC 2。这些CDC的相对分布 在不同的组织类型和病理条件下,亚群不同,表明组织的作用 Pre-CDC分化中的微环境。组织微环境中的哪些因素可能调节这一点 然而,对这一过程仍然知之甚少。我们的初步研究表明,CDC 1分化是 通过将谷氨酰胺代谢转化为谷氨酸盐,由氨基酸谷氨酰胺的局部可用性调节。 谷氨酰胺的摄取和利用在快速增殖的细胞中或在分解代谢应激期间显著增加, 潜在地产生谷氨酰胺缺乏的局部微环境。因此,我们假设代谢 组织中的适应通过调节谷氨酰胺水平改变局部CDC 1分化。在这一建议中,我们寻求 了解CDC 1分化的哪些步骤受谷氨酸及其基础分子的调节 机制我们将集中在基因表达的表观遗传调控和氧化应激作为潜在的 谷氨酸盐介导这种效应的途径。从拟议的工作中发现的结果可能会打开新的 将组织代谢适应与其免疫微环境联系起来的研究路线。

项目成果

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Malay Haldar其他文献

Malay Haldar的其他文献

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{{ truncateString('Malay Haldar', 18)}}的其他基金

Delineating how nucleic acid sensing in tumor cells regulate anti-tumor immune responses
描述肿瘤细胞中的核酸传感如何调节抗肿瘤免疫反应
  • 批准号:
    10626284
  • 财政年份:
    2023
  • 资助金额:
    $ 32.5万
  • 项目类别:
Regulation of antigen presenting cells in the tumor microenvironment by retinoic acid
视黄酸对肿瘤微环境中抗原呈递细胞的调节
  • 批准号:
    10307073
  • 财政年份:
    2018
  • 资助金额:
    $ 32.5万
  • 项目类别:
Regulation of antigen presenting cells in the tumor microenvironment by retinoic acid
视黄酸对肿瘤微环境中抗原呈递细胞的调节
  • 批准号:
    10524742
  • 财政年份:
    2018
  • 资助金额:
    $ 32.5万
  • 项目类别:
Regulation of antigen presenting cells in the tumor microenvironment by retinoic acid
视黄酸对肿瘤微环境中抗原呈递细胞的调节
  • 批准号:
    10051410
  • 财政年份:
    2018
  • 资助金额:
    $ 32.5万
  • 项目类别:
METABOLIC CONTROL OF TISSUE SPECIFIC MACROPHAGE DIFFERENTIATION
组织特异性巨噬细胞分化的代谢控制
  • 批准号:
    9303241
  • 财政年份:
    2013
  • 资助金额:
    $ 32.5万
  • 项目类别:
METABOLIC CONTROL OF TISSUE SPECIFIC MACROPHAGE DIFFERENTIATION
组织特异性巨噬细胞分化的代谢控制
  • 批准号:
    9074750
  • 财政年份:
    2013
  • 资助金额:
    $ 32.5万
  • 项目类别:
METABOLIC CONTROL OF TISSUE SPECIFIC MACROPHAGE DIFFERENTIATION
组织特异性巨噬细胞分化的代谢控制
  • 批准号:
    8566784
  • 财政年份:
    2013
  • 资助金额:
    $ 32.5万
  • 项目类别:
METABOLIC CONTROL OF TISSUE SPECIFIC MACROPHAGE DIFFERENTIATION
组织特异性巨噬细胞分化的代谢控制
  • 批准号:
    8663189
  • 财政年份:
    2013
  • 资助金额:
    $ 32.5万
  • 项目类别:

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