Cytokine-mediated regulation of ILC2 development and effector functions against gastrointestinal helminths

细胞因子介导的 ILC2 发育和效应功能对胃肠道蠕虫的调节

• 批准号: 319494302
• 负责人: Professor Dr. David Vöhringer
• 金额: --
• 依托单位: Infektionsbiologische Abteilung
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/319494302?language=en
• 关键词: Cytokine; mediated; regulation; ILC2; development

Gastrointestinal helminths infect more than 2 billion people world-wide and cause major socioeconomic problems. The mechanisms of protective immunity against helminths are incompletely understood. Recent studies indicated that type 2 innate lymphoid cells (ILC2s) contribute to protection against the gastrointestinal helminth Nippostrongylus brasiliensis (Nb) in mice. During the first funding period of this priority program we could show that the IL-4/IL-13-induced transcription factor STAT6 plays an important role for proliferation and accumulation of ILC2s in the lung of Nb-infected mice. For the second funding period we propose to identify and functionally characterize STAT6-regulated genes in ILC2s. In addition, we will use fluorescent reporter mice to study the migration of ILC2s and their co-localization with other effector cells during helminth infection. Finally, we will specifically delete IL-4/IL-13 in ILC2s to investigate, whether ILC2s are a non-redundant source for both cytokines during primary and secondary immune responses against helminths. Overall, this project will improve our understanding of tissue localization, effector function and plasticity of ILC2s.

胃肠道蠕虫感染全球超过20亿人，并造成重大的社会经济问题。对蠕虫的保护性免疫机制尚未完全了解。最近的研究表明，2型先天淋巴细胞（ILC 2）有助于保护对胃肠道蠕虫的巴西日本圆线虫（Nb）在小鼠。在该优先计划的第一个资助期内，我们可以证明IL-4/IL-13诱导的转录因子STAT 6在Nb感染小鼠肺中的ILC 2增殖和积累中起重要作用。对于第二个资助期，我们建议在ILC 2中识别和功能性表征STAT 6调控的基因。此外，我们将使用荧光报告小鼠研究ILC 2的迁移及其与其他效应细胞在蠕虫感染过程中的共定位。最后，我们将特别删除ILC 2中的IL-4/IL-13，以研究ILC 2在针对蠕虫的初次和二次免疫应答期间是否是两种细胞因子的非冗余来源。总的来说，这个项目将提高我们对ILC 2的组织定位，效应器功能和可塑性的理解。