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.
项目摘要
美国2400万哮喘患者中有一半以上受到过敏性哮喘的影响。白细胞介素4(IL 4)和13
已知IL-13在过敏性哮喘的致病性中起重要作用。他们的生殖系缺失
一种常见的受体,即白细胞介素-4受体α(IL-4 R α),可提供完全的保护,
哮喘提示其不可或缺的作用。因此,阻断IL 4 R α的药理学药物目前是
用于治疗人类过敏性哮喘的临床试验然而,反应并不十分
这可能是由于对新募集的IL 4 R α携带细胞类型的靶向效率低下,
过敏性哮喘的发病机制。这是因为IL 4 R α介导的信号传导在细胞类型特异性中的作用。
过敏性哮喘仍不清楚。鉴定使用IL 4 R α介导的信号传导的关键细胞类型
因此,在过敏性哮喘致病表现中,
过敏性哮喘该提案的总体目标是描述IL 4 R α信号传导的细胞特异性作用。
嗜酸性粒细胞募集和过敏性哮喘,并确定细胞来源和分子身份,
气道(气道和肺泡)中过敏性炎症的可溶性和囊泡结合介质。
与专家建立了杰出的合作关系,包括哮喘专家,外泌体专家,
蛋白质组学专家、分子病理学家、嗜酸性粒细胞生物学专家和IL 4 R α生物学专家。
创新的工具,包括新的转基因小鼠品系,已经开发出来,这将允许一个可行的,
生产性调查。我们的中心假设是,骨髓特异性IL-4 R α信号传导对于
嗜酸性粒细胞的募集和过敏性哮喘相关结果的表现,以及外泌体携带嗜酸性粒细胞,
嗜酸性粒细胞募集的介质。这一假设将在三个具体目标下进行检验。目标1将测试
髓系IL 4 R α对嗜酸性粒细胞募集至关重要的假设;在目标2中,我们将检验这一假设
在混合过敏原激发模型中,髓系IL 4 R α对过敏性哮喘的结局至关重要。这些发现
我们的研究将对我们对疾病病理生理学的机械理解产生变革性的影响。
过敏性哮喘最终,我们的发现可能会应用于细胞特异性治疗的发展
对抗过敏性气道和其他嗜酸性粒细胞疾病。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Yogesh Saini其他文献
Yogesh Saini的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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
- 批准号:
10598728 - 财政年份:2023
- 资助金额:
$ 22.09万 - 项目类别:
Modulation of RNA Binding Proteins in Xenobiotic-induced Hepatotoxicity
RNA 结合蛋白在异生素诱导的肝毒性中的调节
- 批准号:
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:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 22.09万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 22.09万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 22.09万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 22.09万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 22.09万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 22.09万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 22.09万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 22.09万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 22.09万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 22.09万 - 项目类别:
Grant-in-Aid for Early-Career Scientists