HISTAMINE-INDEPENDENT MAST CELL NERVE INTERACTIONS IN ALLERGY
过敏中不依赖组胺的肥大细胞神经相互作用
基本信息
- 批准号:9908041
- 负责人:
- 金额:$ 38.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-05-12 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:Adrenal Cortex HormonesAffectAfferent NeuronsAllergicAllergic ConjunctivitisAllergic DiseaseAntihistaminesAxonBehavioralCalciumCell DegranulationChronicClinicalClinical TreatmentCommunicationCyclosporineDataDevelopmentDrug TargetingEczemaFamilyFiberG-Protein-Coupled ReceptorsGenerationsGenesGeneticHistamineHumanHypersensitivityImaging TechniquesKnowledgeLigandsMediatingMolecularMolecular GeneticsMucous MembraneMusNeuraxisNeurodermatitisNeuronsOpioidPathogenesisPathway interactionsPeptidesPeripheralPharmaceutical PreparationsPharmacologyPhysiologicalPlayPreventionProductivityPruritusQuality of lifeRefractoryRoleSensorySignal TransductionSkinSpecificitySpinal CordSpinal GangliaStructure of trigeminal ganglionSymptomsTestingTherapeuticTissue membraneTransgenic MiceTranslatingUrticariabasebehavioral responsebehavioral studyexperimental studygenetic approachhuman subjectimaging approachin vivoin vivo evaluationinnovationmast cellneuropeptide FFnovelnovel therapeutic interventionpain signalpreventreceptorreconstitutionrelating to nervous systemside effect
项目摘要
Itch is a primary symptom of many allergic conditions, and severely affects the quality of life and
productivity. Primary sensory neurons residing in the trigeminal ganglia and dorsal root ganglia (DRG) play an
essential role in the generation of allergic itch. These neurons detect endogenous itch-inducing molecules
(pruritogens) via a group of itch receptors on their peripheral axons in the skin or mucosal membrane tissues,
and transmit signals to the spinal cord via their central axons. In contrast to the well-studied histamine
pathway, histamine-independent itch pathways in allergic itch remain poorly defined. Previously, we identified
several novel itch receptors within a large family of G-protein‒coupled receptors called Mrgprs. We found that
several Mrgprs recognize distinct pruritogens, and mediate histamine-independent itch. Our latest results
indicate that Mrgprs are required for mast cell-mediated allergic itch. This proposal aims to uncover the
underlying mechanisms. We will test whether Mrgprs mediate the interaction between mast cells and primary
sensory fibers in allergic itch using molecular, genetic and imaging approaches in Aim 1. Furthermore, we will
identify the endogenous Mrgpr ligands released by mast cells upon degranulation in Aim 2. In Aim 3, we seek
to translate our discoveries from mice to humans. Human Mrgprs do not form clear orthologous pairs with
mouse Mrgprs. Their role in itch is therefore unclear. Based on our preliminary data, we hypothesize that
human MrgprX1 mediates neuronal and behavioral response to mast cell-mediated allergy, which will be tested
in Aim 3. These studies will reveal the neural basis underlying allergic itch and will have a significant impact on
both the study of itch pathogenesis and the clinical treatment of itch.
瘙痒是许多过敏性疾病的主要症状,严重影响生活质量,
生产力位于三叉神经节和背根神经节(DRG)的初级感觉神经元起着重要的作用。
在过敏性瘙痒的产生中起重要作用。这些神经元检测内源性瘙痒诱导分子
通过皮肤或粘膜组织中其外周轴突上的一组瘙痒受体,
并通过它们的中央轴突将信号传输到脊髓。与研究充分的组胺相反,
尽管组胺非依赖性瘙痒通路在过敏性瘙痒中的作用尚不明确。此前,我们发现
G蛋白偶联受体大家族中的几种新的瘙痒受体,称为Mrkidney。我们发现
几种Mrsal识别不同的致敏原,并介导组胺非依赖性瘙痒。我们的最新结果
表明肥大细胞介导过敏性瘙痒需要Mrs12。这项提案旨在揭示
基本机制。我们将测试Mrs12是否介导肥大细胞和原发性肥大细胞之间的相互作用。
过敏性瘙痒中的感觉纤维使用分子,遗传和成像方法在目的1中。此外,我们将
鉴定Aim 2中肥大细胞脱粒后释放的内源性Mrgpr配体。在目标3中,我们寻求
将我们的发现从小鼠转化为人类。人类的精子不能与
老鼠先生。因此,它们在瘙痒中的作用尚不清楚。根据我们的初步数据,我们假设,
人MrgprX1介导对肥大细胞介导变态反应的神经元和行为反应,这将被测试
目标3。这些研究将揭示过敏性瘙痒的神经基础,并将对
无论是瘙痒发病机制的研究,还是瘙痒的临床治疗。
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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Qin Liu其他文献
Qin Liu的其他文献
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{{ truncateString('Qin Liu', 18)}}的其他基金
CRISPR/Cas9-based gene editing approaches for the treatment of USH2A-associated diseases
基于 CRISPR/Cas9 的基因编辑方法用于治疗 USH2A 相关疾病
- 批准号:
10626831 - 财政年份:2022
- 资助金额:
$ 38.13万 - 项目类别:
CRISPR/Cas9-based gene editing approaches for the treatment of USH2A-associated diseases
基于 CRISPR/Cas9 的基因编辑方法用于治疗 USH2A 相关疾病
- 批准号:
10446571 - 财政年份:2022
- 资助金额:
$ 38.13万 - 项目类别:
The Neural Mechanism of Respiratory Allergies and Infections
呼吸道过敏和感染的神经机制
- 批准号:
10405559 - 财政年份:2021
- 资助金额:
$ 38.13万 - 项目类别:
The Neural Mechanism of Respiratory Allergies and Infections
呼吸道过敏和感染的神经机制
- 批准号:
10279722 - 财政年份:2021
- 资助金额:
$ 38.13万 - 项目类别:
The Neural Mechanism of Respiratory Allergies and Infections
呼吸道过敏和感染的神经机制
- 批准号:
10612424 - 财政年份:2021
- 资助金额:
$ 38.13万 - 项目类别:
HISTAMINE-INDEPENDENT MAST CELL NERVE INTERACTIONS IN ALLERGY
过敏中不依赖组胺的肥大细胞神经相互作用
- 批准号:
9160145 - 财政年份:2016
- 资助金额:
$ 38.13万 - 项目类别:
Integration of Biomarker Signatures from Peripheral Blood for Diagnosis, Prognosis, Remission and Recurrence of Lung Cancer
整合外周血生物标志物特征用于肺癌的诊断、预后、缓解和复发
- 批准号:
9904543 - 财政年份:2016
- 资助金额:
$ 38.13万 - 项目类别:
Integration of Biomarker Signatures from Peripheral Blood for Diagnosis, Prognosis, Remission and Recurrence of Lung Cancer
整合外周血生物标志物特征用于肺癌的诊断、预后、缓解和复发
- 批准号:
10376913 - 财政年份:2016
- 资助金额:
$ 38.13万 - 项目类别:
HISTAMINE-INDEPENDENT MAST CELL NERVE INTERACTIONS IN ALLERGY
过敏中不依赖组胺的肥大细胞神经相互作用
- 批准号:
9272358 - 财政年份:2016
- 资助金额:
$ 38.13万 - 项目类别:
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