Imprinting of nasal Th2 cell trafficking during allergic sensitization
过敏致敏过程中鼻部 Th2 细胞运输的印记
基本信息
- 批准号:9334098
- 负责人:
- 金额:$ 24.38万
- 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:2016-08-17 至 2018-07-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAgonistAllergensAllergicAllergic DiseaseAllergic rhinitisCD4 Positive T LymphocytesCellsChemicalsChronicClinicalCollaborationsDendritic CellsDevelopmentDiseaseEconomic BurdenEpithelialEventGPR2 geneGenerationsGenomicsGoalsHealthHome environmentHomingHumanHypersensitivityIgEImmunizationIndividualInflammationInflammatoryInstitutesLocationLungLymphoid TissueMediatingMolecularMolecular ProfilingMusNasal EpitheliumNatureNoseOrganPathogenesisPathologicPathway interactionsPeriodicityPhenotypePlayRecruitment ActivityRecurrenceRegulationResearchRhinitisRoleRouteSkinSmall IntestinesStructure of mucous membrane of noseSurfaceT cell regulationT-LymphocyteTestingTherapeuticTissuesUnited Statesairborne allergenallergic responsecell motilitychemokine receptorchronic rhinosinusitiscosthealth economicsimprintin vivo Modelinsightmigrationmouse modelnovelnovel therapeuticspublic health relevancereceptorreceptor expressionrespiratoryresponsesocioeconomicstraffickingvaccine delivery
项目摘要
DESCRIPTION (provided by applicant): Allergic rhinitis is a chronic inflammatory disease of the upper airways that affects approximately 60million people in the United States and is associated with significant socioeconomic costs. Disease is caused by atopic sensitization to aeroallergens in the nasal passages resulting in IgE-mediated clinical signs. Allergic responses are driven by CD4+ Th2 cells and the transfer of these cells is sufficient to induce disease. The induction and recruitment of allergen-specific Th2 cells to the nasal mucosa could have a significant impact on promoting rhinitis, yet little is known regarding the regulation or homing requirements of these cells. We hypothesize that Th2 cell migration to the nasal mucosa is governed by the expression of specific trafficking receptors that are imprinted by nasal dendritic cells. Due to its location, the nasal-associated lymphoid tissue likely plays a crucial role, which
remains to be fully elucidated. We will use mouse models and human clinical tissues to identify the nasal trafficking profile and the mechanisms that regulate it. We will define the chemokine receptor requirements for Th2 cell homing to and motility within the nasal mucosa in response to local allergen sensitization in mice. Findings will be corroborated by ex vivo phenotypic studies in human nasal tissues from controls or subjects with chronic rhinosinusitis. The mechanistic events that underlie the imprinting will focus on the role of tissue dendritic cells. Understanding
the molecular mechanisms of the cellular trafficking requirements of the nasal mucosa is of direct clinical importance and will inform on new avenues for the treatment of allergic diseases. Our eventual goal is to exploit our mechanistic insights to modulate the tissue-tropic trafficking profiles induced in allergen-specific nasal CD4+ T cells to interfere with their migration and curtail the cyclic nature of recurrent Th2-driven rhinitis.
描述(由申请人提供):过敏性鼻炎是一种上呼吸道慢性炎症性疾病,影响美国约6000万人,并与显著的社会经济成本相关。疾病是由对鼻道中的空气过敏原的特应性致敏引起的,导致IgE介导的临床体征。过敏反应是由CD 4 + Th 2细胞驱动的,这些细胞的转移足以诱发疾病。鼻粘膜的变应原特异性Th2细胞的诱导和募集可能对促进鼻炎产生显著影响,但关于这些细胞的调节或归巢要求知之甚少。我们假设Th2细胞迁移到鼻粘膜是由鼻树突状细胞印记的特定贩运受体的表达所控制的。由于其位置,鼻相关淋巴组织可能起着关键作用,
还有待于充分阐明。我们将使用小鼠模型和人类临床组织来确定鼻腔运输概况和调节它的机制。我们将定义趋化因子受体对Th2细胞归巢和在小鼠局部过敏原致敏后鼻粘膜内运动的要求。将通过对来自对照或慢性鼻窦炎受试者的人鼻组织进行的离体表型研究来证实这些发现。作为印记基础的机械事件将集中在组织树突状细胞的作用上。理解
鼻粘膜的细胞运输需求的分子机制具有直接的临床重要性,并将为治疗过敏性疾病提供新的途径。我们的最终目标是利用我们的机制的见解,以调节过敏原特异性鼻CD4+ T细胞诱导的组织嗜性运输概况,干扰他们的迁移和削减复发性Th2驱动的鼻炎的周期性。
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)
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Bas Baaten其他文献
Bas Baaten的其他文献
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{{ truncateString('Bas Baaten', 18)}}的其他基金
T cell immunity to influenza virus in the aged nasal mucosa
老化鼻粘膜中T细胞对流感病毒的免疫
- 批准号:
8160981 - 财政年份:2011
- 资助金额:
$ 24.38万 - 项目类别:
T cell immunity to influenza virus in the aged nasal mucosa
老化鼻粘膜中T细胞对流感病毒的免疫
- 批准号:
8324215 - 财政年份:2011
- 资助金额:
$ 24.38万 - 项目类别:
T cell immunity to influenza virus in the aged nasal mucosa
老化鼻粘膜中T细胞对流感病毒的免疫
- 批准号:
8520147 - 财政年份:2011
- 资助金额:
$ 24.38万 - 项目类别:
T cell immunity to influenza virus in the aged nasal mucosa
老化鼻粘膜中T细胞对流感病毒的免疫
- 批准号:
8723031 - 财政年份:2011
- 资助金额:
$ 24.38万 - 项目类别:
The role of MMP activity in T cells during influenza virus pathogenesis
T细胞中MMP活性在流感病毒发病过程中的作用
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7640779 - 财政年份:2008
- 资助金额:
$ 24.38万 - 项目类别:
The role of MMP activity in T cells during influenza virus pathogenesis
T细胞中MMP活性在流感病毒发病过程中的作用
- 批准号:
7511774 - 财政年份:2008
- 资助金额:
$ 24.38万 - 项目类别:
The role of MMP activity in T cells during influenza virus pathogenesis
T细胞中MMP活性在流感病毒发病过程中的作用
- 批准号:
7917897 - 财政年份:2008
- 资助金额:
$ 24.38万 - 项目类别:
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