Function and Differentiation
功能与差异化
基本信息
- 批准号:10886165
- 负责人:
- 金额:$ 86.68万
- 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:2023-09-08 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAcuteAddressAffectAirway DiseaseAllergensAntibodiesAreaAsthmaB-LymphocytesBCL6 geneBindingBlood VesselsBone MarrowCD4 Positive T LymphocytesCellsCharacteristicsClinicalComplexDataDermatophagoides pteronyssinusDevelopmentDisease modelDisparity populationDoseEffector CellEragrostisExposure toExtrinsic asthmaFamily memberGenerationsGenetic TranscriptionGenomicsGoalsHelper-Inducer T-LymphocyteHeterogeneityHumanIgEImmune TargetingImmunotherapyIncidenceInflammationInflammatoryInfluenzaInterleukin-1Interleukin-10Interleukin-13Interleukin-2Interleukin-4Interleukin-5Knockout MiceKnowledgeLearningLoxP-flanked alleleLungLymphoidMaintenanceMeasurableMediatingMemoryMethodsMicroscopyModelingMolecularMusPathogenesisPathologicPathologyPeptide/MHC ComplexPeptidesPersonsPopulationPopulation HeterogeneityProcessProductionProteinsPyroglyphidaeRecurrenceReporterResearchResolutionSignal TransductionStructure of parenchyma of lungSystemT-Cell ReceptorTechniquesTh1 CellsTh2 CellsTimeTissuesairway inflammationallergic airway inflammationassociated symptomasthmaticasthmatic patientcytokinedesignimmunopathologyimmunoregulationinducible Creinnovationinterestinterleukin-21lymphoid organmagnetic beadsmemory CD4 T lymphocytemigrationmouse modelnovelpreventprogenitorprogrammed cell death protein 1programsreceptorresponsetherapy developmenttooltranscription factor
项目摘要
Project Summary/Abstract
Asthma is an inflammatory disease of the airways characterized by acute, intermittent and recurrent episodes of
inflammation that can be induced by a specific allergen. CD4+ T cells contribute to this process by producing the
Type 2 cytokines IL-4, IL-5, and IL-13 and inducing B cell production of IgE in response to T cell receptor (TCR)
recognition of allergen peptides bound to MHCII molecules on host cells. In both murine models of disease and
asthmatic patients, quiescent allergen peptide:MHCII (pMHCII)-specific CD4+ memory T cells can persist in
lungs and lymphoid organs long after resolution of inflammation. Upon subsequent exposure to allergen, CD4+
memory T cells rapidly drive asthma-induced immunopathology making these cells attractive targets for allergen-
specific immune modulation. Little is known, however, about the function and maintenance of Th2 memory cells
that orchestrate the asthmatic response due to the challenge of tracking small populations of CD4+ T cells that
express allergen pMHCII: specific TCRs. To address this lack of knowledge, we produced an MHCII tetramer
containing a peptide from the Der p1 protein of the house dust mite (HDM), Dermatophagoides pteronyssinus,
the most common cause of atopic asthma. Using this tetramer and a novel magnetic bead-based cell enrichment
method of our design, we have found that IL-2 dependent, functionally heterogeneous populations of Th2 tissue
resident memory cells reside in the lung for long periods of time. The central hypothesis of this application is that
these distinct yet synergistic populations of Th2 “effector Trm” and B cell helping “Tfh Trm” contribute to asthma
pathogenesis in unique ways. The goals of this proposal are to identify the molecular and cellular mechanisms
that lead to Th2 Trm cell heterogeneity and determine how these cells persist in different regions of the lung.
This innovative approach could provide the means for targeting specific pathologic functions of memory Th2
cells by immunotherapy or eliminating them altogether.
项目总结/文摘
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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{{ truncateString('MARION PEPPER', 18)}}的其他基金
The Development and Function of Plasmodium-specific memory B cells
疟原虫特异性记忆 B 细胞的发育和功能
- 批准号:
10062845 - 财政年份:2016
- 资助金额:
$ 86.68万 - 项目类别:
The Development and Function of Plasmodium-specific memory B cells
疟原虫特异性记忆 B 细胞的发育和功能
- 批准号:
9235529 - 财政年份:2016
- 资助金额:
$ 86.68万 - 项目类别:
The differentiation and function of CD4+ Th2 cells during allergen-induced asthma
过敏原诱发哮喘过程中CD4 Th2细胞的分化和功能
- 批准号:
8994262 - 财政年份:2014
- 资助金额:
$ 86.68万 - 项目类别:
The differentiation and function of CD4+ Th2 cells during allergen-induced asthma
过敏原诱发哮喘过程中CD4 Th2细胞的分化和功能
- 批准号:
8910831 - 财政年份:2014
- 资助金额:
$ 86.68万 - 项目类别:
The differentiation and function of CD4+ Th2 cells during allergen-induced asthma
过敏原诱发哮喘过程中CD4 Th2细胞的分化和功能
- 批准号:
8719697 - 财政年份:2014
- 资助金额:
$ 86.68万 - 项目类别:
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