Eosinophil functions in allergic gastrointestinal diseases
嗜酸性粒细胞在过敏性胃肠道疾病中的作用
基本信息
- 批准号:9900740
- 负责人:
- 金额:$ 38.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-11-01 至 2022-02-28
- 项目状态:已结题
- 来源:
- 关键词:Abdominal PainAdrenal Cortex HormonesAdultAffectAllergensAllergicAnatomyAntigen-Presenting CellsAntigensAutomobile DrivingCD4 Positive T LymphocytesCell physiologyChildClinical PathologyDataDeglutition DisordersDevelopmentDiarrheaDiseaseDisease ManagementElemental DietsFailure to ThriveFoodFood AversionFrequenciesFunctional disorderGastrointestinal DiseasesGastrointestinal tract structureGoalsHome environmentHumanHumoral ImmunitiesIgEImmuneImmune responseImmunoglobulin GImmunologicsIn VitroInflammatoryIntestinesKnowledgeLamina PropriaLarge IntestineLeftLeukocytesLinkMediatingModelingMusOralPathogenesisPathogenicityPathway interactionsPatientsPharmacologyPrevalenceProcessPublishingQuality of lifeRefluxResearchRoleSignal TransductionSiteSmall IntestinesT-LymphocyteTestingTimeTissuesTransgenic MiceTreatment EfficacyUnited States National Institutes of HealthVomitingairborne allergenearly satietyefficacy testingeosinophilexperimental studyfood allergengastrointestinalgenetic approachgenetic manipulationhuman diseaseimmunoregulationin vivoin vivo Modelinsightmigrationmouse modelnotch proteinnovelpreventpsychologicsocialsymptom treatmenttargeted treatment
项目摘要
Project Summary
Eosinophilic gastrointestinal disorders (EGIDs) are a group of inflammatory diseases triggered by food or aero-
allergens and characterized by an excessive accumulation and persistence of eosinophils within intestinal
tissues and a Th2-dominant immune response. Despite a worldwide increase in prevalence, the natural
disease course of EGIDs is unknown, and treatment options limited to food allergen avoidance and oral
corticosteroids. EGID symptoms and treatments carry heavy social and psychological tolls, particularly in
affected children. Eosinophils are innate immune leukocytes that constitutively home to lamina propria of the
small and large intestine in the steady-state. Fundamental factors that govern excessive eosinophil
accumulation and persistence within gastrointestinal tissues in EGID patients, and mechanisms whereby
intestinal tissue-resident eosinophils might engage food or aero-allergens and participate in EGID
pathogenesis remain speculative. At the core of this proposal are our two novel findings that: 1) Identify Notch
signaling as a core pathway that orchestrates eosinophil migration and persistence within tissues; and 2)
Demonstrate intestinal eosinophils capture intestinal lumen-derived antigen through a process requiring
antigen-specific IgG and eosinophil-expressed FcγRIII in vivo, constitutively express antigen presenting cell
machinery, and co-localize with T cells following oral allergen challenge. A logical extension of our published
and preliminary data, Aim I of this R01 proposal defines the mechanisms whereby Notch signaling regulates
eosinophil migration and survival within tissues and tests the efficacies of targeting eosinophil-expressed Notch
receptors in preventing EGIDs in vivo. Fully supported by our preliminary data, experiments in Aim II extend
our findings that non-IgE humoral immunity provides a direct link between food allergen triggers and tissue
eosinophils to test a new paradigm whereby intestinal eosinophils engage in antigen-driven degranulation and
direct antigen presenting cell functions that impact the immunopathogenesis of EGIDs by affecting the local
repertoire and spatial arrangement of CD4+ T cells. This proposal utilizes a number of genetic manipulations in
Aims I and II to systematically test our hypotheses in vivo using three antigenically and anatomically distinct
models of EGIDs. In a complementary parallel approach, Aim III utilizes eosinophils isolated from human ileal
tissues and humanized transgenic mice to confirm the direct relevance of our data to human disease, and to
evaluate the fidelity of the mouse as a model for antigen-driven functions of human intestinal eosinophils.
项目总结
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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Lisa Ann Spencer其他文献
Lisa Ann Spencer的其他文献
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{{ truncateString('Lisa Ann Spencer', 18)}}的其他基金
Cellular and molecular mechanisms of mucosal organ crosstalk in allergic diseases
过敏性疾病中粘膜器官串扰的细胞和分子机制
- 批准号:
10615150 - 财政年份:2022
- 资助金额:
$ 38.88万 - 项目类别:
Cellular and molecular mechanisms of mucosal organ crosstalk in allergic diseases
过敏性疾病中粘膜器官串扰的细胞和分子机制
- 批准号:
10418019 - 财政年份:2022
- 资助金额:
$ 38.88万 - 项目类别:
Notch signaling-mediated functions of airway eosinophils in lung disease
Notch信号介导的气道嗜酸性粒细胞在肺部疾病中的功能
- 批准号:
7783163 - 财政年份:2010
- 资助金额:
$ 38.88万 - 项目类别:
Notch signaling-mediated functions of airway eosinophils in lung disease
Notch信号介导的气道嗜酸性粒细胞在肺部疾病中的功能
- 批准号:
8207983 - 财政年份:2010
- 资助金额:
$ 38.88万 - 项目类别:
Notch signaling-mediated functions of airway eosinophils in lung disease
Notch信号介导的气道嗜酸性粒细胞在肺部疾病中的功能
- 批准号:
8594256 - 财政年份:2010
- 资助金额:
$ 38.88万 - 项目类别:
Notch signaling-mediated functions of airway eosinophils in lung disease
Notch信号介导的气道嗜酸性粒细胞在肺部疾病中的功能
- 批准号:
8402994 - 财政年份:2010
- 资助金额:
$ 38.88万 - 项目类别:
Notch signaling-mediated functions of airway eosinophils in lung disease
Notch信号介导的气道嗜酸性粒细胞在肺部疾病中的功能
- 批准号:
8015213 - 财政年份:2010
- 资助金额:
$ 38.88万 - 项目类别:














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