Novel collagen V-reactive natural Th17 cells in hypoxic pulmonary hypertension

缺氧性肺动脉高压中新型胶原 V 反应性天然 Th17 细胞

基本信息

项目摘要

Hypoxic pulmonary hypertension (PH) is a progressive and often fatal consequence of chronic lung diseases, chronic exposure to high altitude and acute lung injury. We have demonstrated that TH17 cells, a pro-inflammatory T helper (TH) cell (CD4+) subset, are localized in the perivascular region of pulmonary arteries. These cells contribute to CH-induced PH. However, whether immunity to self- antigens contributes to disease progression is unknown. Type V collagen (col V) is normally sequestered within the lung interstitium and therefore, hidden from the immune system. Hypoxia could lead to exposure of col V and be a source of antigen. Col V cellular immunity contributes to TH17- dependent obliterative bronchiolitis post-lung transplant, atherosclerosis and interstitial lung fibrosis. However, it is unknown whether colV cellular immunity plays a role in the TH17 cell-dependent perivascular inflammation that contributes to CH-induced PH and the mechanism of TH17 cells homing. It is also unknown if this TH17 cells belong to the natural occurring (nTH17) subset. Therefore, we propose the novel hypothesis that nTH17-mediated PH develops as a result of increased col V-reactive nTH17 cells and reduced peripheral tolerance to col V. We also propose that this mechanism requires nTH17 cell trafficking to the perivascular region under the guidance of C-C motif chemokine ligand 2 (CCL2)/C-C chemokine receptor type 2 (CCR2) signaling. We will pursue the following aims: Specific Aim 1: To identify lung-associated self-antigens induced or exposed by CH. Hypothesis: Col V is a lung-associated self-antigen uncovered by CH that triggers nTH17 cell-mediated perivascular inflammation. Specific Aim 2: To identify the mechanism of nTH17 cell homing to the perivascular region in response to CH. Hypothesis: CCL2/CCR2 signaling drives nTH17 cell homing to the perivascular region in response to CH. Specific Aim 3: To determine the contribution of loss of peripheral tolerance to self-antigens in PH. Hypothesis: A loss in the normal balance between col V-reactive nTH17 cells and nTregs due to nTreg transition to an nTH17 phenotype contributes to the development of PH. Completion of these studies will identify the self-antigens or neo-antigens exposed by CH, determine triggers for nTH17 cell-homing to the pulmonary perivascular region, and the role of peripheral tolerance in this pathway. This groundbreaking study will also facilitate the development of therapies to selectively inhibit the generation of autoreactive T cells and their trafficking to the site of inflammation without affecting the capacity of the host to mount a proper inflammatory response to pathogens.
缺氧性肺动脉高压(PH)是慢性肺疾病的一种进行性且往往致命的后果 慢性高原暴露和急性肺损伤。我们已经证明,TH 17 细胞,一种促炎性T辅助细胞(TH)(CD 4+)亚群,位于血管周围区域, 肺动脉这些细胞有助于CH诱导的PH。 抗原对疾病进展的贡献是未知的。V型胶原蛋白(col V)通常是 被隔离在肺结核中,因此对免疫系统是隐藏的。低氧可 导致暴露于col V并成为抗原来源。Col V细胞免疫有助于TH 17- 肺移植后依赖性闭塞性细支气管炎、动脉粥样硬化和间质性肺纤维化。 然而,尚不清楚colV细胞免疫是否在TH 17细胞依赖性免疫中起作用。 血管周围炎症导致CH诱导的PH和TH 17细胞归巢的机制。 目前还不清楚这种TH 17细胞是否属于天然存在的(nTH 17)亚群。所以我们 提出了一种新的假设,即nTH 17介导的PH是由于col V反应性增加而发展的。 nTH 17细胞和降低的外周对col V的耐受性。 在C-C基序趋化因子配体2的指导下nTH 17细胞向血管周围区域的运输 (CCL 2)/C-C趋化因子受体2型(CCR 2)信号传导。我们将努力实现以下目标: 具体目的1:鉴定CH诱导或暴露的肺相关自身抗原。 是一种未被CH覆盖的肺相关自身抗原,其触发nTH 17细胞介导的血管周围 炎症 具体目的2:确定nTH 17细胞归巢到血管周围区域的机制, 假设:CCL 2/CCR 2信号传导驱动nTH 17细胞归巢到血管周围区域, 回答CH。 具体目标3:确定PH中外周耐受丧失对自身抗原的贡献。 假设:由于nTreg,col V反应性nTH 17细胞和nT细胞之间的正常平衡丧失 向nTH 17表型的转变有助于PH的发展。 完成这些研究将确定CH暴露的自身抗原或新抗原, nTH 17细胞归巢到肺血管周围区域的触发因素,以及外周血淋巴细胞的作用。 这条路上的宽容。这项开创性的研究也将促进治疗方法的发展 选择性地抑制自身反应性T细胞的产生及其运输到免疫缺陷部位, 炎症而不影响宿主的能力,以建立适当的炎症反应, 病原体

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 }}

Laura V Gonzalez Bosc其他文献

Laura V Gonzalez Bosc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('Laura V Gonzalez Bosc', 18)}}的其他基金

NFATc3 in chronic hypoxic pulmonary hypertension
NFATc3 在慢性缺氧性肺动脉高压中的作用
  • 批准号:
    7839262
  • 财政年份:
    2009
  • 资助金额:
    $ 37.88万
  • 项目类别:
NFATc3 in chronic hypoxic pulmonary hypertension
NFATc3 在慢性缺氧性肺动脉高压中的作用
  • 批准号:
    7534997
  • 财政年份:
    2007
  • 资助金额:
    $ 37.88万
  • 项目类别:
NFATc3 in chronic hypoxic pulmonary hypertension
NFATc3 在慢性缺氧性肺动脉高压中的作用
  • 批准号:
    7746406
  • 财政年份:
    2007
  • 资助金额:
    $ 37.88万
  • 项目类别:
NFATc3 in chronic hypoxic pulmonary hypertension
NFATc3 在慢性缺氧性肺动脉高压中的作用
  • 批准号:
    7367250
  • 财政年份:
    2007
  • 资助金额:
    $ 37.88万
  • 项目类别:
NFATc3 in chronic hypoxic pulmonary hypertension
NFATc3 在慢性缺氧性肺动脉高压中的作用
  • 批准号:
    8197297
  • 财政年份:
    2007
  • 资助金额:
    $ 37.88万
  • 项目类别:

相似海外基金

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:
    $ 37.88万
  • 项目类别:
    Training 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:
    $ 37.88万
  • 项目类别:
    Standard Grant
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:
    $ 37.88万
  • 项目类别:
    Standard 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:
    $ 37.88万
  • 项目类别:
    Fellowship
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:
    $ 37.88万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
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:
    $ 37.88万
  • 项目类别:
    Research Grant
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:
    $ 37.88万
  • 项目类别:
    Studentship
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:
    $ 37.88万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 37.88万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 37.88万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了