Mechanisms of Allergen-induced Type 2 Immunity

过敏原诱导的 2 型免疫机制

基本信息

  • 批准号:
    10516908
  • 负责人:
  • 金额:
    $ 59.57万
  • 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:
    2019-11-01 至 2028-04-30
  • 项目状态:
    未结题

项目摘要

The long-term objective of this grant is to investigate how airway exposure to natural allergens leads to development of type 2 immunity and allergic diseases. Exaggerated type 2 immune responses are implicated in a wide variety of disorders ranging from asthma to food allergy. Traditionally, CD4+ type 2 helper T (Th2) cells that produce interleukin (IL)-4, IL-5, and IL-13 have been considered major players in directing the pathophysiology of these diseases, such as airway eosinophilia and IgE antibody production. During the previous funding period of this MERIT Award, we have made major progress in all three Aims. We found that allergen- specific T follicular helper (Tfh) cells and tissue-resident memory (Trm) cells play distinct roles in allergic immune responses. Specifically, Tfh cells promoted production of allergen-specific IgE antibodies and development of acute anaphylaxis while Th2-type Trm cells likely play a role in allergen-induce type 2 cytokine production and eosinophilic inflammation in mucosal tissues. Here we request a 5-year extension of the MERIT Award to continue studying the immunologic mechanism of type 2 immunity. We will finalize and submit at least 4 manuscripts that are described in the progress report. We will extend the studies of the previous funding period and define how allergen exposure mediates various immunologic and clinical phenotypes of allergic diseases. In Aim 1, we will examine the the roles of Th2-type Trm cells in mediating type 2 cytokine production and eosinophilic inflammation in airway mucosa. We will leverage mouse models and use parabiosis and immunologic and genetic approaches to critically define the functions of Trm cells and their regulatory mechanisms. In Aim 2, we will examine how lung T resident helper (Trh) cells mediate IgE antibody production and inflammation in mucosal tissues. Our preliminarily data show the presence of CD4+PD-1+FR4+ Trh cells, a new subset of Tfh-like cells, in the lungs of mice exposed to allergens. We will use mouse genetic approaches to characterize this new cell type and understand its roles in type 2 immunity. In Aim 3, we continue collaborating with Dr. Shiv Kale, and ask a fundamental question why certain allergens robustly induce type 2 immunity. We will take a fungal functional genomic approach and study the roles of - galactosidases produced by fungus Alternaria. Together, the studies in these aims will define the central mechanisms underlying the development and regulation of type 2 immunity to airborne allergens and will provide an immunologic explanation regarding various clinical phenotypes of allergic diseases. Ultimately, these studies will characterize key cellular pathway(s) and molecule(s) involved in allergic immune responses, allowing identification of critical targets for development of novel therapeutic strategies to treat or to prevent asthma and allergic diseases. RELEVANCE (See instructions): Patients with asthma and allergic diseases have persistent respiratory health problems and exaggerated immune responses to common inhaled allergens. This project will investigate how exposure to natural allergens causes, prolongs, and intensifies these diseases.
该基金的长期目标是研究气道暴露于天然过敏原如何导致 2型免疫和过敏性疾病的发展。夸大的2型免疫反应与 从哮喘到食物过敏的各种疾病。传统上,CD 4 + 2型辅助性T(Th 2)细胞 产生白细胞介素(IL)-4,IL-5和IL-13的细胞被认为是指导 这些疾病的病理生理学,如气道嗜酸性粒细胞增多和IgE抗体产生。前一 在今次优异奖的资助期内,我们在三个目标方面均取得重大进展。我们发现了过敏原- 特异性滤泡辅助性T细胞(Tfh)和组织驻留记忆性T细胞(Trm)在过敏性免疫中发挥不同的作用 应答具体地说,Tfh细胞促进过敏原特异性IgE抗体的产生和过敏原的发展。 急性过敏反应,而Th 2型Trm细胞可能在变应原诱导的2型细胞因子产生中起作用, 粘膜组织中的嗜酸性炎症。在此,我们要求将MERIT奖延长5年, 继续研究2型免疫的免疫机制。我们将最终确定并提交至少4份 进度报告中描述的手稿。我们会延长上一个资助期的研究 并定义过敏原暴露如何介导过敏性疾病的各种免疫学和临床表型。在 目的1,我们将研究Th 2型Trm细胞在介导2型细胞因子产生中的作用, 气道粘膜嗜酸性粒细胞炎症。我们将利用小鼠模型, 免疫学和遗传学方法来严格定义Trm细胞的功能及其调节 机制等在目标2中,我们将研究肺T驻留辅助细胞(Trh)如何介导IgE抗体的产生 和粘膜组织中的炎症。我们的初步数据显示存在CD 4 +PD-1+ FR 4 + Trh细胞, 在暴露于过敏原的小鼠肺中,发现了一种新的Tfh样细胞亚群。我们将使用小鼠遗传学方法, 描述这种新的细胞类型,并了解其在2型免疫中的作用。在目标3中,我们继续合作 Shiv Kale博士,并提出一个基本问题,为什么某些过敏原强烈诱导2型免疫。我们 将采用真菌功能基因组学方法,研究真菌产生的β-半乳糖苷酶的作用 链格孢总之,这些目标的研究将确定发展的核心机制, 和调节2型免疫对空气中的过敏原,并将提供一个免疫学解释, 过敏性疾病的各种临床表型。最终,这些研究将表征关键的细胞通路, 以及参与过敏性免疫反应的分子,从而可以识别发展的关键目标 新的治疗策略来治疗或预防哮喘和过敏性疾病。 相关性(参见说明): 哮喘和过敏性疾病患者有持续的呼吸道健康问题,并夸大 对常见吸入性过敏原的免疫反应这个项目将调查如何暴露于自然 过敏原导致、加重和加重这些疾病。

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 }}

Hirohito Kita其他文献

Hirohito Kita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('Hirohito Kita', 18)}}的其他基金

Allergen-induced extracellular DNA in type 2 immunity
2 型免疫中过敏原诱导的细胞外 DNA
  • 批准号:
    10708997
  • 财政年份:
    2022
  • 资助金额:
    $ 59.57万
  • 项目类别:
Allergen-induced extracellular DNA in type 2 immunity
2 型免疫中过敏原诱导的细胞外 DNA
  • 批准号:
    10580884
  • 财政年份:
    2022
  • 资助金额:
    $ 59.57万
  • 项目类别:
Type 2 Innate Lymphoid Cells and Asthma
2 型先天淋巴细胞与哮喘
  • 批准号:
    10219332
  • 财政年份:
    2019
  • 资助金额:
    $ 59.57万
  • 项目类别:
Mechanisms of IL-33 secretion in allergic diseases
IL-33分泌在过敏性疾病中的机制
  • 批准号:
    10063933
  • 财政年份:
    2019
  • 资助金额:
    $ 59.57万
  • 项目类别:
Mechanisms of Allergen-induced Type 2 Immunity
过敏原诱导的 2 型免疫机制
  • 批准号:
    10394292
  • 财政年份:
    2019
  • 资助金额:
    $ 59.57万
  • 项目类别:
Type 2 Innate Lymphoid Cells and Asthma
2 型先天淋巴细胞与哮喘
  • 批准号:
    10063304
  • 财政年份:
    2019
  • 资助金额:
    $ 59.57万
  • 项目类别:
Mechanisms of Allergen-induced Type 2 Immunity
过敏原诱导的 2 型免疫机制
  • 批准号:
    10133504
  • 财政年份:
    2019
  • 资助金额:
    $ 59.57万
  • 项目类别:
Mechanisms of Allergen-induced Type 2 Immunity
过敏原诱导的 2 型免疫机制
  • 批准号:
    9899933
  • 财政年份:
    2019
  • 资助金额:
    $ 59.57万
  • 项目类别:
Mechanisms of Allergen-induced Type 2 Immunity
过敏原诱导的 2 型免疫机制
  • 批准号:
    10182141
  • 财政年份:
    2019
  • 资助金额:
    $ 59.57万
  • 项目类别:
Mechanisms of IL-33 secretion in allergic diseases
IL-33分泌在过敏性疾病中的机制
  • 批准号:
    10044045
  • 财政年份:
    2019
  • 资助金额:
    $ 59.57万
  • 项目类别:

相似海外基金

Measurement of serum IgE and identification of allergens in seafood allergic patients
海鲜过敏患者血清IgE测定及过敏原鉴定
  • 批准号:
    21K13490
  • 财政年份:
    2021
  • 资助金额:
    $ 59.57万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Mechanisms of augmentation of contact allergic reactions by irritants and contact allergens
刺激物和接触性过敏原增强接触性过敏反应的机制
  • 批准号:
    335858052
  • 财政年份:
    2017
  • 资助金额:
    $ 59.57万
  • 项目类别:
    Research Grants
Elucidation of conformational epitopes of peanut allergens essential for allergic reactions
阐明过敏反应所必需的花生过敏原的构象表位
  • 批准号:
    8970024
  • 财政年份:
    2015
  • 资助金额:
    $ 59.57万
  • 项目类别:
Environmental allergens affect the function of allergic inflammatory cells
环境过敏原影响过敏性炎症细胞的功能
  • 批准号:
    26860758
  • 财政年份:
    2014
  • 资助金额:
    $ 59.57万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Effects of allergens on dendritic cell function in allergic asthma
过敏原对过敏性哮喘树突状细胞功能的影响
  • 批准号:
    nhmrc : 303161
  • 财政年份:
    2004
  • 资助金额:
    $ 59.57万
  • 项目类别:
    NHMRC Project Grants
IImmune Tolerance Network: Airborne Allergens and Allergic Rhintitis
II免疫耐受网络:空气中的过敏原和过敏性鼻炎
  • 批准号:
    8348615
  • 财政年份:
    2001
  • 资助金额:
    $ 59.57万
  • 项目类别:
IImmune Tolerance Network: Airborne Allergens and Allergic Rhintitis
II免疫耐受网络:空气中的过敏原和过敏性鼻炎
  • 批准号:
    8522031
  • 财政年份:
    2001
  • 资助金额:
    $ 59.57万
  • 项目类别:
IImmune Tolerance Network: Airborne Allergens and Allergic Rhintitis
II免疫耐受网络:空气中的过敏原和过敏性鼻炎
  • 批准号:
    8730013
  • 财政年份:
    2001
  • 资助金额:
    $ 59.57万
  • 项目类别:
ASPERGILLUS ALLERGENS AND ALLERGIC ASPERGILLOSIS
曲霉过敏原和过敏性曲霉病
  • 批准号:
    6137243
  • 财政年份:
    1998
  • 资助金额:
    $ 59.57万
  • 项目类别:
ASPERGILLUS ALLERGENS AND ALLERGIC ASPERGILLOSIS
曲霉过敏原和过敏性曲霉病
  • 批准号:
    2462172
  • 财政年份:
    1998
  • 资助金额:
    $ 59.57万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了