Type 2 Innate Lymphoid Cells and Asthma

2 型先天淋巴细胞与哮喘

基本信息

  • 批准号:
    10219332
  • 负责人:
  • 金额:
    $ 47.33万
  • 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:
    2019-11-27 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT This project's long-term goal is to understand asthma's immunological mechanisms. Airway inflammation in patients with asthma is generally characterized by increased lymphocytes producing type 2 cytokines. However, the mechanisms involved in persistent and/or recurrent production of type 2 cytokines in the airways are not entirely understood. Notable progress regarding the mechanisms of type 2 immunity has been made in the past several years. Group 2 innate lymphoid cells (ILC2s) that rapidly produce large quantities of type 2 cytokines have been identified and are implicated in the innate arm of type 2 immunity. More recent findings suggest the ability of ILC2s to regulate the adaptive arm of immunity and their high degree of plasticity. Thus, the primary objective of this renewal application is to translate these new discoveries in the basic science of ILC2s to the immunologic mechanisms of asthma. We will test the hypothesis that ILC2s play a vital role in persistent and recurrent airway inflammation in asthma. In Aim 1, we will determine the roles of lung ILC2s in a chronic airway inflammation model in mice. By using a model in which mice are repeatedly exposed to natural airborne allergens, we will dissect the roles for ILC2s and Th2-type CD4+ T cells in chronic airway inflammation. In Aim 2, we will elucidate the genetic and functional plasticity of lung ILC2s in mice. The immune system of mice housed in a regular specific pathogen- free environment is similar to human neonates. Through the use of a recently developed novel mouse model that replicates a human adult-like immune system, we will investigate the functional plasticity of lung ILC2s in that environment and how their abilities to promote type 2 inflammation are modulated. In Aim 3, we will investigate the roles of ILC2s in a chronic airway disease in humans. In patients, chronic rhinosinusitis (CRS) is often associated with asthma. By using an established clinical protocol to evaluate CRS patients during a natural exacerbation of the disease, we will investigate how functions of ILC2s are regulated dynamically in the disease process. This application integrates mechanistic studies in mice and a proof-of-concept study in humans. It represents collaborative efforts among basic science and translational immunologists and clinician investigators. The tools and technical expertise necessary to accomplish this project are in place. Therefore, the proposed studies will likely provide fundamental information regarding type 2 airway inflammation recurrence and persistence in patients with asthma and ILC2s involvement. Clarification of the immunological mechanisms involved in the disease process will lead to development of novel strategies for the prevention and treatment of asthma and related chronic airway disorders.
项目总结/摘要 该项目的长期目标是了解哮喘的免疫机制。气道炎症 在哮喘患者中,通常以产生2型细胞因子的淋巴细胞增加为特征。 然而,参与持续和/或复发的2型细胞因子产生的机制, 气道并不完全清楚。 在过去几年中,关于2型免疫机制的研究取得了显著进展。 快速产生大量2型细胞因子的第2组先天性淋巴细胞(ILC 2)已被发现, 被鉴定并与2型免疫的先天性臂有关。最近的研究结果表明, ILC 2调节免疫的适应性臂及其高度可塑性。因此,主要目标 这项更新申请的目的是将ILC 2基础科学中的这些新发现转化为 哮喘的免疫机制我们将检验ILC 2在持续性和非持续性免疫中发挥重要作用的假设。 哮喘的复发性气道炎症。 在目的1中,我们将确定肺ILC 2在小鼠慢性气道炎症模型中的作用。通过 使用小鼠反复暴露于天然空气过敏原的模型,我们将剖析 ILC 2s和Th 2型CD 4 + T细胞在慢性气道炎症中的作用在目标2中,我们将阐明遗传和 小鼠肺ILC 2的功能可塑性。把老鼠的免疫系统放在一个特定的病原体里- 自由环境与人类新生儿相似。通过使用最近开发的新型小鼠模型 复制人类成人样免疫系统,我们将研究肺ILC 2的功能可塑性, 以及它们促进2型炎症的能力是如何调节的。在目标3中,我们 研究ILC 2在人类慢性气道疾病中的作用。慢性鼻窦炎(CRS) 通常与哮喘有关。通过使用已建立的临床方案来评估CRS患者, 疾病的自然恶化,我们将研究ILC 2的功能是如何动态调节的, 疾病的过程。 该应用整合了小鼠的机制研究和人类的概念验证研究。它 代表了基础科学和转化免疫学家和临床医生之间的合作努力 investigators.完成这一项目所需的工具和技术专长已经到位。因此,我们认为, 所提出的研究将可能提供有关2型气道炎症的基本信息 哮喘和ILC 2参与的患者的复发和持续性。免疫学澄清 参与疾病过程的机制将导致新的预防策略的发展, 以及治疗哮喘和相关的慢性气道疾病。

项目成果

期刊论文数量(19)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
IL-33-Responsive Group 2 Innate Lymphoid Cells Are Regulated by Female Sex Hormones in the Uterus.
IL-33: biological properties, functions, and roles in airway disease.
  • DOI:
    10.1111/imr.12552
  • 发表时间:
    2017-07
  • 期刊:
  • 影响因子:
    8.7
  • 作者:
    Drake LY;Kita H
  • 通讯作者:
    Kita H
Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune response in mice.
  • DOI:
    10.1111/all.12446
  • 发表时间:
    2014-10
  • 期刊:
  • 影响因子:
    12.4
  • 作者:
    Drake LY;Iijima K;Kita H
  • 通讯作者:
    Kita H
IL-33 and thymic stromal lymphopoietin mediate immune pathology in response to chronic airborne allergen exposure.
How are airborne allergens remembered by the immune system?
免疫系统如何记住空气中的过敏原?
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Hirohito Kita其他文献

Hirohito Kita的其他文献

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{{ 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:
    $ 47.33万
  • 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:
    $ 47.33万
  • 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:
    $ 47.33万
  • 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:
    $ 47.33万
  • 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:
    $ 47.33万
  • 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:
    $ 47.33万
  • 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:
    $ 47.33万
  • 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:
    $ 47.33万
  • 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:
    10516908
  • 财政年份:
    2019
  • 资助金额:
    $ 47.33万
  • 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:
    $ 47.33万
  • 项目类别:

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