IRF4 and immunity to influenza infection

IRF4和流感感染免疫力

基本信息

批准号：
9011502
负责人：
Jie Sun
金额：
$ 11.4万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
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：
2015-02-10 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9011502
关键词：
Antiviral Agents Apoptosis Avidity B-Lymphocytes Binding Biological CD4 Positive T Lymphocytes CD8B1 gene Cell Cycle Arrest Cellular Immunity Coupled Cytotoxic T-Lymphocytes Data Defect Development Disease Outbreaks Economics Elderly Future Gene Expression Generations Genes Goals Health Helper-Inducer T-Lymphocyte Human Humoral Immunities IRF4 gene Immune Immune response Immunity Immunization Individual Infant Infection Influenza Influenza A Virus, H5N1 Subtype Influenza A Virus, H7N9 Subtype Influenza vaccination Knowledge Lower Respiratory Tract Infection Mediating Metabolism Molecular Molecular Profiling Morbidity - disease rate Mus Neonatal Pattern Physiological Play Population Prevention Reporting Role Shapes Signal Transduction Source Structure of germinal center of lymph node T cell response T-Lymphocyte Testing Therapeutic United States Vaccines Viral Virus Virus Diseases base combat design global health human mortality improved influenza virus vaccine influenzavirus killings neonatal human pandemic disease pandemic influenza pathogen response restoration seasonal influenza social tool transcription factor vaccine efficacy

项目摘要

DESCRIPTION (provided by applicant): This proposal is based on our recent studies that IRF4 plays an essential role in sustaining cytotoxic T lymphocyte (CTL) expansion and effector differentiation during influenza infection. In this application, we will further investigate the celular mechanisms by which IRF4 controls the quantity and quality of CTL responses during influenza infection. In addition, we hypothesize that the defective IRF4 expression in infant T cells constitutes a major barrier for the efficient development of both cellular and humoral immunity in infants following immunization. We believe that the manipulation of IRF4 expression and function may serve as a potential strategy to boost both humoral and cellular immunity in infants. Two specific aims are proposed: Aim1: To elucidate the mechanisms through which IRF4 modulates the quantity and quality of anti-viral CTL responses. Aim2: To determine the role of impaired IRF4 expression in T cells in infant immunity. Relevance statement Influenza virus is a tremendous source of morbidity and mortality for the human population, especially in infants. CD8 cytotoxic T lymphocytes (CTLs) play an important role in the control of influenza virus infections and the generation of a cross-reactive CTL-based vaccine remains a viable vaccine option for the prevention/amelioration of future pandemics. However, current understanding the molecular mechanisms regulating the efficient development of CD8 T cell-mediated immunity to influenza infection is still largely elusive. The successful completion of thi application thus will significant advance our understanding on the induction of effective CTL responses during primary influenza infection. Furthermore, the knowledge generated from these studies will improve our understanding of the molecular mechanisms underlying the defects in both cellular and humoral immunity in infants. In addition, we expect that this application will establish principles that could be utilized in the future to improve the efficacy of influenza and other pathogen vaccines in infants.

描述（由申请人提供）：该提案基于我们最近的研究，即IRF4在流感感染期间维持细胞毒性T淋巴细胞（CTL）扩增和效应分化中发挥重要作用。在本申请中，我们将进一步研究其细胞机制。 IRF4 控制流感感染过程中 CTL 反应的数量和质量。此外，我们发现婴儿 T 细胞中的 IRF4 表达缺陷是婴儿随后发展细胞和体液有效免疫的主要障碍。我们认为，操纵 IRF4 表达和功能可能作为增强婴儿体液和细胞免疫的潜在策略：目的 1：阐明 IRF4 调节抗抗体数量和质量的机制。 -病毒 CTL 反应目标 2：确定 T 细胞中 IRF4 表达受损在婴儿免疫中的作用相关性声明流感病毒是人类发病率和死亡率的一个巨大来源，尤其是。 CD8 细胞毒性 T 淋巴细胞 (CTL) 在控制流感病毒感染中发挥着重要作用，基于交叉反应性 CTL 的疫苗仍然是预防/改善未来流行病的可行疫苗选择。对调节 CD8 T 细胞介导的流感感染有效免疫发展的分子机制的了解在很大程度上仍是难以捉摸的，因此该应用的成功完成将显着推进我们对原发性流感感染期间有效 CTL 反应诱导的理解。知识产生这些研究的结果将提高我们对婴儿细胞和体液免疫缺陷的分子机制的理解。此外，我们预计该应用将建立未来可用于提高流感和其他病原体功效的原理。婴儿疫苗。