Neuroimmune Control of Allergic Immunity
过敏性免疫的神经免疫控制
基本信息
- 批准号:10625256
- 负责人:
- 金额:$ 59.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:Afferent NeuronsAllergensAllergicAllergic DiseaseAntigensB-LymphocytesBacteriaBasophilsCCR8 geneCell CommunicationCell MaturationCell physiologyCellsCellular ImmunologyCellular NeurobiologyCutaneousDataDendritic CellsDendritic cell activationDermalDermisDetectionDevelopmentDiseaseEndowmentFoundationsGoalsHealthIgEImmuneImmune responseImmune systemImmunityImmunizationImmunologicsIn VitroInnate Immune ResponseInnate Immune SystemInterleukin-4LaboratoriesLicensingLymphoid CellMusNervous SystemNeuroimmuneNeuronsNeuropeptidesPapainPapayaPathway interactionsPatientsPeptide HydrolasesPlayPopulationPrevalenceProductionPruritusResearchRoleSensorySignal TransductionSkinSubstance PT-LymphocyteTRPV1 geneTestingTh2 CellsUnited StatesVenomsadaptive immune responsecell motilitychronic itchdraining lymph nodeenvironmental allergenexperiencefungusimmune activationimprovedin vivoinsightmast cellmigrationneurotransmitter releasenovelnovel therapeutic interventionnovel therapeuticspain sensationpreventprogramsrelease factorresponsesensortherapeutic developmenttool
项目摘要
Project Summary/Abstract
One central paradox in the initiation of allergic immunity is that although dendritic cells are necessary for the
initiation of allergic immune responses, dendritic cells are activated in vivo by allergen immunization, but not
directly in vitro by allergens. This indicates that another cell may act upstream of dendritic cells to act as the
initial allergen sensor. Our long-term goal is to understand how the innate immune system is activated by
allergens to initiate the allergic immune response. Given that 40% of the United States population suffers from
one or more allergic diseases and that the prevalence of allergic disease continues to increase worldwide, we
believe there is an urgent health need to understand how allergic diseases are initiated. We recently found that
sensory neurons are directly activated by allergens in vivo and in vitro, leading to the release of Substance P
that activates the migration of Th2-skewing dendritic cells through their expression of MRPGPRA1. Our central
hypothesis is that sensory neurons are the initial sensors of allergens and that their interactions with innate
immune cells both promote sensory neuronal responsiveness to allergens and allows sensory neurons to
initiate the allergic immune response. Building upon recent breakthroughs detailing sensory neurons involved
in allergen sensing, dendritic cell subsets that respond to allergens, and mechanisms of allergic-skewing
dendritic cell migration, we propose to integrate tools of cellular immunology and neurobiology to gain a
fundamental understanding of neuroimmune interactions that promote allergic immune activation. Using these
tools, we propose to test our central hypothesis in two specific aims: (1) determine the mechanisms by which
allergen-stimulated sensory neurons interact with and initiate dendritic cell activation, and (2) identify how T
cells control sensory neuron activation by allergens. Aim 1 will examine the interactions between sensory
neurons and dendritic cells, and the requirement for Substance P and MRGPRA1 in these interactions. Aim 2
will address how a novel subset of dermal T cells may endow or promote the responsiveness of sensory
neurons to allergens. These studies will lay the groundwork for the development of therapeutic strategies to
prevent initial allergic sensitization (Aim 1), treat chronic itch diseases (Aim 2), and prevent polysensitization in
patients with pre-existing allergic disease (Aims 1 & 2).
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)
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Caroline Lauren Sokol其他文献
Caroline Lauren Sokol的其他文献
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{{ truncateString('Caroline Lauren Sokol', 18)}}的其他基金
Age-Related Alterations in Neuro-Immune Recognition of Allergens
过敏原神经免疫识别中与年龄相关的变化
- 批准号:
10373431 - 财政年份:2022
- 资助金额:
$ 59.63万 - 项目类别:
Age-Related Alterations in Neuro-Immune Recognition of Allergens
过敏原神经免疫识别中与年龄相关的变化
- 批准号:
10559576 - 财政年份:2022
- 资助金额:
$ 59.63万 - 项目类别:
The Role of Innate Immune Cell Trafficking in Th2 Differentiation
先天免疫细胞运输在 Th2 分化中的作用
- 批准号:
9302656 - 财政年份:2016
- 资助金额:
$ 59.63万 - 项目类别:
The Role of Innate Immune Cell Trafficking in Th2 Differentiation
先天免疫细胞运输在 Th2 分化中的作用
- 批准号:
9923557 - 财政年份:2016
- 资助金额:
$ 59.63万 - 项目类别:
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