IL-15 和 PIM 激酶指导肠上皮内淋巴细胞的代谢程序

IL-15 and PIM kinases direct the metabolic programming of intestinal intraepithelial lymphocytes

 

 


关键词:无

细胞类型:淋巴细胞
作者:James OJ, Vandereyken M, Marchingo JM, Singh F, Bray SE, Wilson J, Love AG, Swamy M
出版期刊:《Nature Communications》 2021/7/13

Abstract:

Intestinal intraepithelial lymphocytes (IEL) are an abundant population of tissue-resident T cells that protect and maintain the intestinal barrier. IEL respond to epithelial cell-derived IL-15, which is complexed to the IL-15 receptor α chain (IL-15/Rα). IL-15 is essential both for maintaining IEL homeostasis and inducing IEL responses to epithelial stress, which has been associated with Coeliac disease. Here, we apply quantitative mass spectrometry to IL-15/Rα-stimulated IEL to investigate how IL-15 directly regulates inflammatory functions of IEL. IL-15/Rα drives IEL activation through cell cycle regulation, upregulation of metabolic machinery and expression of a select repertoire of cell surface receptors. IL-15/Rα selectively upregulates the Ser/Thr kinases PIM1 and PIM2, which are essential for IEL to proliferate, grow and upregulate granzyme B in response to inflammatory IL-15. Notably, IEL from patients with Coeliac disease have high PIM expression. Together, these data indicate PIM kinases as important effectors of IEL responses to inflammatory IL-15.

 

文章摘要:

肠上皮内淋巴细胞 (IEL) 是丰富的组织驻留 T 细胞群,可保护和维持肠道屏障。 IEL 对上皮细胞衍生的 IL-15 作出反应,IL-15 与 IL-15 受体 α 链 (IL-15/Rα) 复合。 IL-15 对于维持 IEL 稳态和诱导 IEL 对与乳糜泻相关的上皮应激的反应都是必不可少的。在这里,我们将定量质谱法应用于 IL-15/Rα 刺激的 IEL,以研究 IL-15 如何直接调节 IEL 的炎症功能。 IL-15/Rα 通过细胞周期调节、代谢机制的上调和细胞表面受体的选择库的表达来驱动 IEL 激活。 IL-15/Rα 选择性上调 Ser/Thr 激酶 PIM1 和 PIM2,这对于 IEL 增殖、生长和上调颗粒酶 B 以响应炎症性 IL-15 至关重要。值得注意的是,来自乳糜泻患者的 IEL 具有高 PIM 表达。总之,这些数据表明 PIM 激酶是 IEL 对炎症性 IL-15 反应的重要效应物。

 


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