Elucidating the roles of alveolar macrophage inflammation and self renewal duringinfluenza infection
Elucidating the roles of alveolar macrophage inflammation and self renewal duringinfluenza infection
批准号:
10515526
负责人:
Jie Sun
金额:
$27.07万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
未结题
起止时间:
2020-08-15 至 2025-04-30
中文摘要
摘要/摘要
甲型流感病毒(IAV)对全球健康构成持续威胁。IAV感染尤其成问题
在老年人中,估计接近90%的IAV相关死亡发生在老年人中。肺泡
巨噬细胞(AM)是在肺稳态中重要的主要肺巨噬细胞群体,
抗病毒免疫和组织恢复。AM表现出类似茎的自我更新特征,但也可以迅速地
在刺激时产生促炎介质,这可能会导致肺部
炎症和损伤。目前对AM的调控机制知之甚少
体内增殖和炎症命运决定,以及随后对组织炎症的影响,
IAV感染后恢复。在这个应用中,我们假设b-连环蛋白,HIF 1-a
TCF-4调节AM的自我更新和炎症活性,从而调节肺的
在IAV感染期间炎症和组织修复。此外,我们假设夸大的B-
catenin-HIF 1-a表达决定了AM自我更新和功能中与衰老相关的缺陷,
导致老年宿主感染IAV后严重的肺部疾病和/或有缺陷的肺修复。
提出了三个具体目标。目的1:阐明B-
连环蛋白/HIF 1-a复合物调节AM炎症活性和自我更新,以及随后对
宿主疾病和从IAV感染中恢复。目标2:确定技术合作框架的基本机制,
4在体内平衡期间和IAV后调节AM发育、自我更新和/或炎症
感染目的3:确定AM b-连环蛋白/HIF 1-a轴失调在衰老中的作用。
AM功能和再生的相关缺陷,从而导致严重的IAV相关疾病,
老房东
英文摘要
Summary/Abstract
Influenza A virus (IAV) constitutes an ongoing threat to global health. IAV infection is especially problematic
in aged individuals, with estimated close to 90% IAV-associated deaths occurring in the elderly. Alveolar
macrophages (AMs) are the primary lung macrophage population that are important in lung homeostasis,
anti-viral immunity and tissue recovery. AMs exhibit stem-like features of self-renewal, but also can rapidly
produce pro-inflammatory mediators upon stimulation, which could potentially contribute to pulmonary
inflammation and injury during IAV infection. Little is known currently about the mechanisms modulating AM
proliferative and inflammatory fate decisions in vivo, and the subsequent effects on tissue inflammation and
recovery following IAV infection. In this application, we hypothesize that the interplay of b-catenin, HIF1-a
and TCF-4 modulates AM self-renewal and inflammatory activity, thereby regulating pulmonary
inflammation and tissue repair during IAV infection. Furthermore, we hypothesize that exaggerated b-
catenin-HIF1-a expression dictates the aging-associated defects in AM self-renewal and function, thereby
leading to severe pulmonary diseases and/or defective lung repair following IAV infection in aged hosts.
Three specific Aims are proposed. Aim 1: To elucidate the associated-mechanisms by which b-
catenin/HIF1-a complex modulates AM inflammatory activity and self-renewal, and subsequent effects on
host diseases and recovery from IAV infection. Aim 2: To define the underlying mechanisms by which TCF-
4 regulates AM development, self-renewal and/or inflammation during homeostasis and following IAV
infection. Aim 3: To determine the roles of dysregulated AM b-catenin/HIF1-a axis in contributing to aging-
associated defects in AM function and regeneration, thereby causing severe IAV-associated diseases in
aged hosts.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Uncover mechanisms underlying the development of chronic lung sequelae post COVID-19
-
批准号:10734747
-
项目类别:
-
资助金额:$72.03万
-
财政年份:2023
-
负责人:Jie Sun
-
依托单位:
Determinants of Convalescent and Vaccine-induced Mucosal Specific Immunity to SARS-CoV-2 and Variants of Concern in Children with Asthma
-
批准号:10638521
-
项目类别:
-
资助金额:$70.72万
-
财政年份:2023
-
负责人:Jie Sun
-
依托单位:
Modeling severe respiratory syncytial virus pathogenesis in bronchopulmonarydysplasia
-
批准号:10515456
-
项目类别:
-
资助金额:$19.88万
-
财政年份:2022
-
负责人:Jie Sun
-
依托单位:
Roles of tissue-resident helper T cells in mucosal immunity against influenzainfection
-
批准号:10605297
-
项目类别:
-
资助金额:$61.31万
-
财政年份:2022
-
负责人:Jie Sun
-
依托单位:
Roles of tissue-resident helper T cells in mucosal immunity against influenzainfection
-
批准号:10393621
-
项目类别:
-
资助金额:$61.69万
-
财政年份:2022
-
负责人:Jie Sun
-
依托单位:
Roles of tissue-resident helper T cells in mucosal immunity against influenzainfection
-
批准号:10515543
-
项目类别:
-
资助金额:$51.32万
-
财政年份:2022
-
负责人:Jie Sun
-
依托单位:
COVID-19 competitive revision: BALANCING PROTECTIVE IMMUNITY AND CHRONIC SEQUELAE BY RESIDENT CD8 T CELLS
-
批准号:10224990
-
项目类别:
-
资助金额:$21.16万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Modeling severe respiratory syncytial virus pathogenesis in bronchopulmonary dysplasia
-
批准号:9981352
-
项目类别:
-
资助金额:$23.85万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Balancing protective immunity and chronic sequelae by resident CD8 T cells
-
批准号:9981307
-
项目类别:
-
资助金额:$56.5万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Elucidating the roles of alveolar macrophage inflammation and self renewal duringinfluenza infection
-
批准号:10652322
-
项目类别:
-
资助金额:$45.17万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Mechanisms of influenza viral pathogenesis in normal hosts and hosts with chronic diseases
-
批准号:10198309
-
项目类别:
-
资助金额:$49.41万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Balancing protective immunity and chronic sequelae by resident CD8 T cells
-
批准号:10265754
-
项目类别:
-
资助金额:$40.61万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Elucidating the roles of alveolar macrophage inflammation and selfrenewal during influenza infection
-
批准号:10063352
-
项目类别:
-
资助金额:$45.6万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Roles of tissue-resident helper T cells in mucosal immunity against influenza infection
-
批准号:10065060
-
项目类别:
-
资助金额:$51.5万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Balancing protective immunity and chronic sequelae by resident CD8 T cells
-
批准号:10515461
-
项目类别:
-
资助金额:$56.97万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Elucidating the roles of alveolar macrophage inflammation and self renewal duringinfluenza infection
-
批准号:10425391
-
项目类别:
-
资助金额:$46.32万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Balancing protective immunity and chronic sequelae by resident CD8 T cells
-
批准号:10549833
-
项目类别:
-
资助金额:$56.97万
-
财政年份:2020
-
负责人:Jie Sun
-
依托单位:
Simultaneously boosting both humoral and cellular immunity following vaccination
-
批准号:9401954
-
项目类别:
-
资助金额:$31.98万
-
财政年份:2017
-
负责人:Jie Sun
-
依托单位:
Molecular regulation of protective CD8 immunity against influenza infection
-
批准号:10161713
-
项目类别:
-
资助金额:$3.43万
-
财政年份:2015
-
负责人:Jie Sun
-
依托单位:
Molecular regulation of protective CD8 immunity against influenza infection
-
批准号:10393651
-
项目类别:
-
资助金额:$50.12万
-
财政年份:2015
-
负责人:Jie Sun
-
依托单位:
海外基金