Analysis of the role of the transcription factor IRF4 for cytotoxic T lymphocyte effector function and memory development

转录因子IRF4对细胞毒性T淋巴细胞效应功能和记忆发育的作用分析

• 批准号: 185202009
• 负责人: Professorin Dr. Magdalena Huber
• 金额: --
• 依托单位: Institut für Systemimmunologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/185202009?language=en
• 关键词: Analysis; role; transcription; factor; IRF4

CD8+ T cells contribute to host defense during infection with intracellular pathogens, and in the elimination of tumor cells. After stimulation via their TCR, naïve CD8+ T cells differentiate into effector cytotoxic T lymphocytes (CTLs) which acquire the ability to kill target cells and into memory cells which are responsible for immunity to reinfection. The factors and mechanisms that drive the development of effector and memory CTLs are not completely understood. However, recent evidence suggests that both events are coordinated by a common transcriptional module for CD8+ T and B cells. Extensive studies in B-cells have shown that the transcription factor interferon regulatory factor 4 (IRF4) plays an essential role in B-cell effector differentiation and may be involved in this module. In contrast, in CD8+ T cells only a single report exists that analyzed CTL function in IRF4 deficient mice and suggested a critical role of IRF4 for CD8+ T cell effector development. To understand the mechanisms governing CTL differentiation, we intend to analyze the function of IRF4 in CD8+ T cells more closely in vitro and in vivo during the infection of mice with the intracellular bacterium Listeria monocytogenes. The results obtained by this project will provide deeper insights of the transcriptional network governing CD8+ T cell effector and memory differentiation. Improved understanding of the role of IRF4 could lead to new types of immunotherapy that modulate IRF4 levels to alter effector and/or memory CD8+ T cell differentiation.

CD 8 + T细胞在细胞内病原体感染期间有助于宿主防御，并有助于消除肿瘤细胞。在通过其TCR刺激后，幼稚CD 8 + T细胞分化为效应细胞毒性T淋巴细胞（CTL），其获得杀死靶细胞的能力，并分化为负责对再感染免疫的记忆细胞。驱动效应和记忆CTL发展的因素和机制尚未完全了解。然而，最近的证据表明，这两个事件是协调一个共同的转录模块的CD 8 + T和B细胞。在B细胞中的广泛研究表明，转录因子干扰素调节因子4（IRF 4）在B细胞效应分化中起着重要作用，并可能参与该模块。相比之下，在CD 8 + T细胞中，仅存在分析IRF 4缺陷小鼠中的CTL功能并表明IRF 4对于CD 8 + T细胞效应子发育的关键作用的单一报告。为了了解CTL分化的机制，我们打算在体外和体内用细胞内细菌单核细胞增生李斯特菌感染小鼠期间更密切地分析IRF 4在CD 8 + T细胞中的功能。该项目所获得的结果将为控制CD 8 + T细胞效应和记忆分化的转录网络提供更深入的见解。对IRF 4作用的进一步理解可能导致新型免疫疗法，其调节IRF 4水平以改变效应和/或记忆CD 8 + T细胞分化。

项目成果

IRF4 provides rations for cytotoxic CD8(+) T cell soldiers.

IRF4 为细胞毒性 CD8( ) T 细胞士兵提供口粮

• DOI: 10.1016/j.immuni.2013.10.008
• 发表时间: 2013
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Huber M;Lohoff M
• 通讯作者: Lohoff M

The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells

• DOI: 10.1073/pnas.1309378110
• 发表时间: 2013-09-10
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Raczkowski, Friederike;Ritter, Josephine;Huber, Magdalena
• 通讯作者: Huber, Magdalena