Defining the role of lymphotoxin signaling in viral-induced lung immunopathology
定义淋巴毒素信号在病毒诱导的肺免疫病理学中的作用
基本信息
- 批准号:9361449
- 负责人:
- 金额:$ 16.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-02-01 至 2018-01-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Lung pathology is a significant cause of the morbidity and mortality associated with acute respiratory virus infection. Respiratory viruses, such as influenza virus not only cause damage to the epithelium, but activate immune defense mechanisms. Although these immune mechanisms are employed to destroy and remove infected cells in an attempt to clear the virus, they can also promote lung pathology. However, the key cellular and molecular mechanisms that regulate the balance between protection and tissue damage during acute viral infection remain poorly understood. This lack of knowledge severely limits the development of novel therapies to treat the disease. Therefore, understanding the fundamental mechanisms whereby respiratory viral infection induces lung damage is critical for the development of improved therapies for treatment of disease. Our exciting and intriguing preliminary results suggest that the lymphotoxin beta receptor, LTßR, a member of the TNFR superfamily, promotes influenza-associated lung damage. The overall objective of this proposal is to define how LTβR controls lung damage associated with influenza infection. Our working hypothesis is that LTβR signaling in respiratory epithelial cells inhibits mucus production during influenza infection allowing for elevated viral replication and increased lung damage. To test this hypothesis, we propose two specific aims. In Aim 1, we will use biochemical and genetic approaches to determine the impact of LTβR signaling on mucus production and viral replication. In Aim 2, we will test that LTβR signaling in respiratory epitheial cells is essential to promote lung immunopathology during influenza infection. We propose that LTβR signaling in respiratory epithelial cells promotes viral replication and induction of potent inflammatory responses which cause severe lung damage. Completion of these aims will define the LTβR-dependent mechanisms that contribute to lung damage. The research proposed is significant, because it will provide a deeper understanding of the mechanisms regulating virus-induced immunopathology and will help in developing new immunotherapeutic strategies to control respiratory disease.
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Lymphotoxin in physiology of lymphoid tissues - Implication for antiviral defense.
- DOI:10.1016/j.cyto.2016.08.018
- 发表时间:2018-01
- 期刊:
- 影响因子:3.8
- 作者:Koroleva EP;Fu YX;Tumanov AV
- 通讯作者:Tumanov AV
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Alexei V Tumanov其他文献
Alexei V Tumanov的其他文献
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{{ truncateString('Alexei V Tumanov', 18)}}的其他基金
Defining the role of lymphotoxin signaling in viral-induced lung immunopathology
定义淋巴毒素信号在病毒诱导的肺免疫病理学中的作用
- 批准号:
8994268 - 财政年份:2015
- 资助金额:
$ 16.87万 - 项目类别:
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