Defining the IL-7 niche for local and systemic ILC homeostasis

定义局部和全身 ILC 稳态的 IL-7 生态位

• 批准号: 320279996
• 负责人: Professor Dr. Thomas Schüler
• 金额: --
• 依托单位: Institut für Molekulare und Klinische Immunologie
• 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 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/320279996?language=en
• 关键词: Defining; IL; niche; local; systemic

Cytokine production by non-hematopoietic stromal cells regulates immune cell development and function, e.g. in the BM and in LNs. IL-7 is a classical stromal cell-derived cytokine and is crucial for T and B cell development. Importantly, it also promotes the development and function of ILCs. IL-7 is produced e.g. in the BM and intestine. However, the relative contribution of different IL-7-producing cell types/organs to the modulation of local and systemic ILC responses is still unclear. In order to address this question, we have established and analyzed several tissue-specific IL-7 knockout mice in the first funding period. So far our analyses were mainly focused on the steady state and acute inflammatory conditions. In the next funding period, we would like to extent our analyses to models of colitis-associated colon cancer (CAC). For this purpose, we aim to complement our studies on local and systemic ILC homeostasis in stroma-specific IL-7 knockout mice with our newly established mouse models lacking individual NKp46+ ILC subsets. With the help of both approaches we aim i) to identify those stromal cell types that define the IL-7 niche for ILC homeostasis and function in vivo and ii) to identify those NKp46+ ILCs, which modulate stromal cell function and IL-7-associated CAC-development.

由非造血基质细胞产生的细胞因子调节免疫细胞发育和功能，例如在BM和LN中。IL-7是一种经典的基质细胞衍生的细胞因子，对T和B细胞发育至关重要。重要的是，它还促进了国际法委员会的发展和运作。IL-7例如在BM和肠中产生。然而，不同IL-7产生细胞类型/器官对局部和全身ILC应答的调节的相对贡献仍不清楚。为了解决这个问题，我们在第一个资助期建立并分析了几种组织特异性IL-7基因敲除小鼠。到目前为止，我们的分析主要集中在稳态和急性炎症条件。在下一个资助期，我们希望将我们的分析扩展到结肠炎相关结肠癌（CAC）模型。为此目的，我们的目标是补充我们的研究，局部和全身ILC稳态基质特异性IL-7敲除小鼠与我们新建立的小鼠模型缺乏个别NKp 46 + ILC子集。在这两种方法的帮助下，我们的目标是i）鉴定那些定义IL-7生态位的基质细胞类型，用于ILC体内稳态和功能，以及ii）鉴定那些调节基质细胞功能和IL-7相关的CAC发展的NKp 46 + ILC。