Innate immune regulation of lung inflammation through mitochondrial dynamics
通过线粒体动力学调节肺部炎症的先天免疫
基本信息
- 批准号:10659953
- 负责人:
- 金额:$ 80.95万
- 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:2023-05-02 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:Activities of Daily LivingAdoptive TransferAffectAgeAllergensAsthmaAutomobile DrivingBiochemicalBioenergeticsCatabolismCell physiologyCellsCellular biologyCessation of lifeChemicalsChildClinicalCytokine SignalingDataDevelopmentDiseaseEconomicsEffector CellExposure toFlow CytometryGenerationsGlucoseGlycolysisHumanImaging TechniquesImmuneImmunobiologyImpairmentIndividualInflammationInflammatoryKnockout MiceKnowledgeLinkLungLymphoid CellMetabolicMetabolismMitochondriaMolecularMorphologyMusNutrientPapainPathologicPathway interactionsPeptide HydrolasesPhysiciansPilot ProjectsPopulationProductionPublic HealthPulmonary InflammationRoleScientistSignal TransductionSourceStructure of parenchyma of lungTechniquesTestingTherapeuticTissuesairway inflammationallergic airway inflammationasthmaticasthmatic patientchronic inflammatory lung diseaseconditional knockoutcytokineglucose metabolismglucose uptakeimmunoregulationimprovedinflammatory lung diseaseliquid chromatography mass spectrometrylive cell imaginglung developmentmitochondrial fitnessmitochondrial membranemouse modelnovelpreventresponserestrainttranscriptome sequencing
项目摘要
PROJECT SUMMARY
In the US alone, asthma affects approximately 24 million individuals, 6 million of whom are children under the
age of 18, and is responsible for over 3,000 deaths annually1,2. A population of immune cells, called group 2
innate lymphoid cells (ILC2s), are integral in driving lung inflammatory diseases including asthma through
production of type 2 cytokines in response to tissue `alarmin' cytokine signals. Despite these advances on ILC2
function, there is a fundamental gap in our knowledge of the intracellular pathways that control this pathologic
capacity within pro-inflammatory ILC2s. In new preliminary studies, we uncovered a novel link between
intracellular changes in the structural morphology of ILC2 mitochondria and the pro-inflammatory capacity
within these cells that results in lung airway inflammation. We found that upon exposure to lung tissue
inflammatory signals, ILC2s increased mitochondrial mass and remodeled their mitochondrial morphology
network from a state of elongated `fusion' to fragmented `fission'. Furthermore, we found that inhibition of
fission during a murine model of papain allergen exposure strongly curtailed ILC2 responses and altered their
metabolic programming, thereby resulting in protection from severe lung inflammation. However, despite these
advances, fundamental gaps in knowledge remain about 1) how remodeling of mitochondrial network
morphology affects ILC2-intrinsic airway inflammation and 2) the identification of the metabolic mechanisms by
which mitochondrial dynamics control ILC2 pro-inflammatory function. Here I propose two Aims consisting of
cutting-edge techniques in cellular metabolism and immunobiology to dissect the role of mitochondrial
morphology dynamics in controlling ILC2 metabolic programming and pathological function during murine and
human allergic airway inflammation.
项目摘要
仅在美国,哮喘就影响了大约2400万人,其中600万是儿童,
18岁,每年造成3,000多人死亡1,2。一群免疫细胞,称为第2组
先天性淋巴样细胞(ILC 2)在驱动包括哮喘在内的肺部炎症性疾病中是不可或缺的,
2型细胞因子响应组织“警报”细胞因子信号的产生。尽管ILC 2取得了这些进展,
功能,我们对控制这种病理性的细胞内途径的知识存在根本性的空白。
在促炎ILC 2中的能力。在新的初步研究中,我们发现了一种新的联系,
ILC 2线粒体结构形态和促炎能力的细胞内变化
导致肺部气道炎症。我们发现当暴露在肺组织中时
ILC 2增加线粒体质量并重塑其线粒体形态
网络从拉长的“融合”状态到碎片化的“裂变”状态。此外,我们还发现,
在木瓜蛋白酶过敏原暴露的小鼠模型中的裂变强烈地减少了ILC 2反应,并改变了它们的表达。
代谢编程,从而导致保护免受严重的肺部炎症。然而,尽管有这些
进展,知识的根本差距仍然是关于1)如何重塑线粒体网络
形态学影响ILC 2-内源性气道炎症和2)通过
其线粒体动力学控制ILC 2促炎功能。在此,我提出两个目标,
细胞代谢和免疫生物学的尖端技术来剖析线粒体的作用,
在小鼠和哺乳动物中控制ILC 2代谢编程和病理功能的形态动力学
人类过敏性气道炎症。
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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Laurel Anne Monticelli其他文献
Laurel Anne Monticelli的其他文献
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{{ truncateString('Laurel Anne Monticelli', 18)}}的其他基金
Metabolic regulation of innate lymphoid cell function and airway inflammation
先天淋巴细胞功能和气道炎症的代谢调节
- 批准号:
9647099 - 财政年份:2019
- 资助金额:
$ 80.95万 - 项目类别:
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