Determining the contribution of polyamine biosynthesis to the function of group 3 innate lymphoid cells in the gastrointestinal system
确定多胺生物合成对胃肠道系统第 3 组先天淋巴细胞功能的贡献
基本信息
- 批准号:10252814
- 负责人:
- 金额:$ 3.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:Activities of Daily LivingAdultAffectAgingAnabolismAnti-CD40AntibodiesArginineAutoimmuneAutoimmunityB-LymphocytesBacteriaBiological AssayBody Weight decreasedBromodeoxyuridineCCR6 geneCell physiologyCellsChemicalsChromatinChronicCitrobacterCitrobacter rodentiumColitisColonCrohn&aposs diseaseDL-alpha-DifluoromethylornithineDataDeveloped CountriesDeveloping CountriesDevelopmentDisease MarkerDistalDrug usageEnvironmentEnzymesEpithelialEukaryotaExhibitsFlow CytometryGoalsGranulocyte-Macrophage Colony-Stimulating FactorHistologyHomeostasisHost DefenseHumanImmuneImmunofluorescence MicroscopyImpairmentIn VitroInfectionInflammatoryInflammatory Bowel DiseasesInterleukin-17IntestinesLaboratoriesLightLymphocyteLymphoidLymphoid CellLymphoid FollicleLymphoid TissueMalignant NeoplasmsMeasuresMediatingMetabolicMetabolic PathwayMetabolismModelingMonitorMucous MembraneMusMyeloid CellsNeutrophil InfiltrationOrnithine DecarboxylasePathogenicityPathologyPlayPolyamine Synthesis InhibitionPolyaminesPre-Clinical ModelProductionRag1 MouseResearchResearch ProposalsResistanceRoleSeverity of illnessShapesSignal TransductionSmall IntestinesT-LymphocyteTherapeutic InterventionTissuesTranslationsTumor-infiltrating immune cellsUlcerative Colitiscytokinedietaryenteric infectionenteric pathogenexperimental studyextracellulargastrointestinal systemimmunoregulationin vivointerleukin-22intestinal homeostasismetabolomicsmonocytemouse modelnew therapeutic targetresponsesingle-cell RNA sequencing
项目摘要
Project Summary
The objective of this research proposal is to define the role of polyamines in modulating intestinal innate lymphoid
cell homeostasis. Innate lymphoid cells (ILC) play a crucial role in mucosal barrier integrity and resistance to
pathogenic insult through the integration of environmental signals and rapid secretion of immunoregulatory
cytokines. In the intestine, group 3 ILC (ILC3) are crucial in defense against pathogenic bacterial colonization.
They play significant roles in promoting the barrier function of the epithelium, regulating intestinal myeloid cells,
and inducing the formation of lymphoid tissue within the mucosa to orchestrate intestinal homeostasis. However,
dysregulation of ILC3 drives intestinal autoimmunity and has been associated with chronic inflammatory bowel
diseases (IBD). Although it is known that intestinal lymphocytes make numerous metabolic adaptations in order
to function in the tissue, little is understood about the relationship between cellular metabolism and the various
functions of ILC3. We have integrated single-cell RNA-sequencing data and untargeted metabolomics of
intestinal ILC to identify a significant enrichment of polyamines and polyamine metabolic enzymes in ILC3.
Furthermore, our preliminary data demonstrate a positive role for polyamines in supporting ILC3 proliferation
and function. We propose to 1) evaluate the impact of intracellular polyamines on ILC3 function at steady state
and 2) assess the contribution of ILC3-intrinsic polyamine metabolism in a preclinical model of colitis. We
hypothesize that polyamines positively regulate ILC3 function and thus contribute to the
immunopathological role of ILC3 in colitis.
The proposed research plan will define an ILC3-intrinsic contribution of polyamines in enhancing their activity
and potentiating colitis. If this is the case, these results will further our understanding of the metabolic adaptations
of ILC3 as well as the potential role for targeting these metabolic pathways to treat IBD.
项目摘要
本研究的目的是确定多胺在调节肠道先天淋巴细胞中的作用。
细胞内稳态先天性淋巴样细胞(ILC)在粘膜屏障完整性和抵抗炎症中起着至关重要的作用。
通过整合环境信号和免疫调节因子的快速分泌,
细胞因子在肠道中,第3组ILC(ILC 3)在防御病原性细菌定植中至关重要。
它们在促进上皮屏障功能、调节肠髓样细胞、
并诱导粘膜内淋巴组织的形成以协调肠内稳态。然而,在这方面,
ILC 3的失调驱动肠道自身免疫,并与慢性炎症性肠病相关
疾病(IBD)。虽然我们知道肠道淋巴细胞会进行多种代谢适应,
在组织中发挥作用,对细胞代谢和各种代谢之间的关系知之甚少。
ILC 3的功能。我们整合了单细胞RNA测序数据和非靶向代谢组学,
肠ILC以鉴定ILC 3中多胺和多胺代谢酶的显著富集。
此外,我们的初步数据表明,多胺在支持ILC 3增殖中具有积极作用
和功能我们建议:1)评估稳态下细胞内多胺对ILC 3功能的影响
和2)评估ILC 3-内在多胺代谢在结肠炎临床前模型中的作用。我们
假设多胺正调节ILC 3功能,从而有助于
ILC 3在结肠炎中免疫病理学作用
拟议的研究计划将确定一个ILC 3-内在贡献的多胺在提高其活动
和增强结肠炎如果是这样的话,这些结果将进一步加深我们对代谢适应的理解,
以及靶向这些代谢途径治疗IBD的潜在作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Vincent Peng其他文献
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{{ truncateString('Vincent Peng', 18)}}的其他基金
Determining the contribution of polyamine biosynthesis to the function of group 3 innate lymphoid cells in the gastrointestinal system
确定多胺生物合成对胃肠道系统第 3 组先天淋巴细胞功能的贡献
- 批准号:
10474523 - 财政年份:2020
- 资助金额:
$ 3.2万 - 项目类别:
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