Myeloid Cell Signaling in Allergic Asthma
过敏性哮喘中的骨髓细胞信号转导
基本信息
- 批准号:10341066
- 负责人:
- 金额:$ 22.09万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-01-02 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAffectAllergensAllergicAllergic inflammationAlveolarAsthmaBiological AssayBiologyCellsClinical TrialsCollaborationsComplexDataDevelopmentDiseaseEosinophiliaEpithelialExtrinsic asthmaFibrosisFunctional disorderGene Expression ProfilingGerm LinesHumanIL4 geneInflammation MediatorsInterleukin 4 ReceptorInterleukin-13Interleukin-4InvestigationKnock-outLeadLungMediatingMediator of activation proteinMetaplastic CellModelingMolecularMouse StrainsMucous body substanceMusMyelogenousMyeloid CellsOutcomePathogenesisPathogenicityPathologistPharmaceutical PreparationsPharmacologyPlayProductionProteomicsRoleSignal TransductionSourceSpecialistStressTestingTherapeuticTherapeutic InterventionTransgenic MiceUnited StatesVesicleairway hyperresponsivenessasthmaticcell preparationcell typecytokineeosinophilexosomegenetic signatureinnovationmouse modelnovelpreclinical trialreceptorrecruitresponsetargeted treatmenttherapeutically effectivetool
项目摘要
Project Summary
Allergic asthma affects over half of the 24 million asthmatics in the United States. Interleukins 4 (IL4) and 13
(IL13) are known to play an essential role in the pathogenicity of allergic asthma. Germ-line deletion of their
common receptor, i.e. Interleukin-4 receptor alpha (IL4Rα), provides complete protection against allergic
asthma suggesting its indispensable role. Accordingly, pharmacological agents blocking IL4Rα are currently
under clinical trials for management of human allergic asthma. The responses are, however, not very
promising, perhaps due to the inefficient targeting of a freshly recruited IL4Rα-bearing cell-type involved in the
pathogenesis of allergic asthma. This is because the cell-type specific role of IL4Rα-mediated signaling in
allergic asthma has remained unclear. Identification of a key cell-type that employs IL4Rα-mediated signaling
in pathogenic manifestation of allergic asthma may, therefore, lead to a more effective therapeutic intervention
in allergic asthma. The overall objective of this proposal is to delineate the cell-specific role of IL4Rα signaling
in eosinophil recruitment and allergic asthma and to identify the cellular source and molecular identity of
soluble and vesicle-bound mediators of allergic inflammation in airspaces (airway and alveolar airspaces).
Outstanding collaborations have been established with experts, including an asthma specialist, an exosomes
proteomics specialist, a molecular pathologist, an eosinophil biology expert, and an IL4Rα biology expert.
Innovative tools, including novel transgenic mouse strains, have been developed that will allow a feasible and
productive investigation. Our central hypothesis is that myeloid-specific IL-4Rα signaling is essential for
recruitment of eosinophils and manifestation of allergic asthma-relevant outcomes and that exosomes carry the
mediators of eosinophil recruitment. This hypothesis will be tested under three specific aims. Aim 1 will Test
the hypothesis that myeloid IL4Rα is essential for eosinophil recruitment; in Aim 2 we will Test the hypothesis
that myeloid-IL4Rα is essential for allergic asthma outcomes in a mixed allergen challenge model. The findings
from our studies will have a transformative impact on our mechanistic understanding of the pathophysiology of
allergic asthma. Eventually, our findings may be applied towards the development of cell-specific therapeutics
against allergic airway and other eosinophilic disorders.
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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Yogesh Saini其他文献
Yogesh Saini的其他文献
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{{ truncateString('Yogesh Saini', 18)}}的其他基金
Pathogenesis of mucous cell metaplasia in ozone-exposed airways
臭氧暴露气道粘液细胞化生的发病机制
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10598728 - 财政年份:2023
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Modulation of RNA Binding Proteins in Xenobiotic-induced Hepatotoxicity
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10587498 - 财政年份:2023
- 资助金额:
$ 22.09万 - 项目类别:
Understanding the role of myeloid cells in ozone-induced airway disease
了解骨髓细胞在臭氧引起的气道疾病中的作用
- 批准号:
10337211 - 财政年份:2019
- 资助金额:
$ 22.09万 - 项目类别:
Understanding the role of myeloid cells in ozone-induced airway disease
了解骨髓细胞在臭氧引起的气道疾病中的作用
- 批准号:
10091437 - 财政年份:2019
- 资助金额:
$ 22.09万 - 项目类别:
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