Epidermal Nonpeptidergic Nerves Modulate Cutaneous Immunity
表皮非肽能神经调节皮肤免疫
基本信息
- 批准号:10216987
- 负责人:
- 金额:$ 53.48万
- 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:2020-07-15 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AblationAcuteAfferent NeuronsAgonistAllergic DiseaseAutomobile DrivingCandida albicansCell DegranulationCell physiologyCellsChronicContact hypersensitivityCrotonCutaneousDataDendritic CellsDendritic cell activationDermalDermisDevelopmentDiphtheria ToxinEpidermisEventG-Protein-Coupled ReceptorsGeneticGoalsHaptensHost DefenseIL17 geneImmuneImmune responseImmunityImmunologic TestsImmunosuppressionIndividualInfectionInfectious Skin DiseasesInflammationInflammatoryInnate Immune ResponseInterleukin-17InterruptionIrritantsLasersLinkMechanoreceptorsMediatingModelingMusNerveNeurogenic InflammationNeuroimmuneNeuronsOilsOrganPainPathogenesisPathway interactionsPhenotypePrimatesProductionPruritusResistanceSensorySkinSomatostatinStaphylococcus aureusStimulusTRPV1 geneTestingTh2 CellsTouch sensationWorkafferent nervebasecutaneous sensory neuronsdiphtheria toxin receptorextracellulargain of functionimmune functionin vivoloss of functionmast celloptogeneticspain sensationpathogenresponsesingle-cell RNA sequencingtranscriptomics
项目摘要
Abstract
The skin is a highly innervated organ and contains numerous sensory afferent neurons that
respond to a diverse array of stimuli including touch, pruritogens (inducing itch) and noxious
agents (inducing pain). There are also many skin-resident immune cells including dendritic cells
and mast cells that make direct contact with sensory neurons. It has very recently become
appreciated that cutaneous sensory neurons and skin-resident innate immune cells work
synergistically to initiate local inflammation and host defense. We have previously shown that
TRPV1+ neurons that sense pain are necessary and sufficient for cutaneous innate Type-17
inflammation and host defense against C. albicans. Thus, a neuron subset associated with
painful stimuli is necessary and sufficient to drive a Type-17 immune response which is the
optimal immune response against extracellular pathogens that can cause painful stimuli. We
now propose to test the immunologic potential of nonpeptidergic sensory neurons are that can
be divided based on single cell RNAseq into at least 3 subsets: NP1, NP2, and NP3. The
overall goal of this proposal is to understand the unique contribution of individual subsets of
nonpeptidergic sensory neurons to the modulation of skin immunity. Exploring this neuro-
immune interaction will better define the cellular circuits driving inflammation and allow for the
use of agonists/antagonists that target neuron subsets in order to modulate specific types of
cutaneous immune responses without global immunosuppression. Specifically, we hypothesize
that NP1 sensory nerves function to suppress mast cell activity. We further hypothesize that the
NP2 and NP3 subsets that communicate itch sensation in response to pruritogens also
participate in the development of Type-2 immune responses analogous to TRPV1+ neurons and
Type-17 immune responses. The potential to modulate Th2 and mast cell function makes these
pathways potential key for allergic disease pathogenesis.
摘要
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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Kathryn Marie Albers其他文献
Kathryn Marie Albers的其他文献
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{{ truncateString('Kathryn Marie Albers', 18)}}的其他基金
Epidermal Nonpeptidergic Nerves Modulate Cutaneous Immunity
表皮非肽能神经调节皮肤免疫
- 批准号:
10652420 - 财政年份:2020
- 资助金额:
$ 53.48万 - 项目类别:
Cross-talk between the colon epithelium, colon afferents and sympathetic neurons regulate pain in the normal and inflamed colon
结肠上皮、结肠传入神经和交感神经元之间的串扰调节正常和发炎结肠的疼痛
- 批准号:
10159250 - 财政年份:2020
- 资助金额:
$ 53.48万 - 项目类别:
Molecular and Functional Analysis of Hirschsprung Defects in Humans and Mouse
人类和小鼠先天性巨结肠缺陷的分子和功能分析
- 批准号:
10597975 - 财政年份:2020
- 资助金额:
$ 53.48万 - 项目类别:
Cross-talk between the colon epithelium, colon afferents and sympathetic neurons regulate pain in the normal and inflamed colon
结肠上皮、结肠传入神经和交感神经元之间的串扰调节正常和发炎结肠的疼痛
- 批准号:
10617264 - 财政年份:2020
- 资助金额:
$ 53.48万 - 项目类别:
Cross-talk between the colon epithelium, colon afferents and sympathetic neurons regulate pain in the normal and inflamed colon
结肠上皮、结肠传入神经和交感神经元之间的串扰调节正常和发炎结肠的疼痛
- 批准号:
10399623 - 财政年份:2020
- 资助金额:
$ 53.48万 - 项目类别:
Epidermal Nonpeptidergic Nerves Modulate Cutaneous Immunity
表皮非肽能神经调节皮肤免疫
- 批准号:
10440275 - 财政年份:2020
- 资助金额:
$ 53.48万 - 项目类别:
Epidermal Nonpeptidergic Nerves Modulate Cutaneous Immunity
表皮非肽能神经调节皮肤免疫
- 批准号:
10065774 - 财政年份:2020
- 资助金额:
$ 53.48万 - 项目类别:
Molecular and Functional Analysis of Hirschsprung Defects in Humans and Mouse
人类和小鼠先天性巨结肠缺陷的分子和功能分析
- 批准号:
10386806 - 财政年份:2020
- 资助金额:
$ 53.48万 - 项目类别:
Characterization of epithelial-neural communication
上皮神经通讯的表征
- 批准号:
9240592 - 财政年份:2016
- 资助金额:
$ 53.48万 - 项目类别:
Characterization of epithelial-neural communication
上皮神经通讯的表征
- 批准号:
9898306 - 财政年份:2016
- 资助金额:
$ 53.48万 - 项目类别:
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