CIRI, Centre International de Recherche en Infectiologie - International Center for Infectiology Research, Lyon, France.
Inserm, U1111, Lyon, France.
Eur J Immunol. 2019 May;49(5):677-685. doi: 10.1002/eji.201847721. Epub 2019 Feb 15.
To gain insight into the biology of NK cells, others and we previously identified the NK-cell signature, defined as the set of transcripts which expression is highly enriched in these cells compared to other immune subtypes. The transcript encoding the Serine/threonine/tyrosine kinase 1 (Styk1) is part of this signature. However, the role of Styk1 in the immune system is unknown. Here, we report the generation of a novel transgenic mouse model, in which Styk1 expression is invalidated and replaced by an EGFP reporter cassette. We demonstrated that Styk1 expression is a hallmark of NK cells and other NK1.1 expressing cells such as liver type 1 innate lymphoid cells (ILC1) and NK1.1 γδ T cells. Styk1 expression is maintained by IL-15 in NK cells and negatively correlates with the expression of educating NK-cell receptors. Analysis of phosphorylation levels of mTOR substrates suggested that Styk1 could moderately contribute to the activity of the PI3K/Akt/mTOR pathway. However, Styk1-deficient NK cells develop normally and have normal in vitro and in vivo effector functions. Thus Styk1 expression is a hallmark of NK cells, ILC1 and NK1.1 T cells but is dispensable for their development and immune functions.
为了深入了解 NK 细胞的生物学特性,我们和其他人之前确定了 NK 细胞的特征签名,这一定义为在这些细胞中表达高度富集的一组转录本,与其他免疫亚型相比。编码丝氨酸/苏氨酸/酪氨酸激酶 1(Styk1)的转录本是该特征签名的一部分。然而,Styk1 在免疫系统中的作用尚不清楚。在这里,我们报告了一种新型转基因小鼠模型的产生,其中Styk1 的表达被无效化,并被 EGFP 报告基因盒取代。我们证明了 Styk1 的表达是 NK 细胞和其他 NK1.1 表达细胞(如肝脏 1 型先天淋巴样细胞(ILC1)和 NK1.1 γδ T 细胞)的特征。在 NK 细胞中,IL-15 维持 Styk1 的表达,并与教育性 NK 细胞受体的表达呈负相关。对 mTOR 底物磷酸化水平的分析表明,Styk1 可能适度促进 PI3K/Akt/mTOR 途径的活性。然而,Styk1 缺陷型 NK 细胞正常发育,具有正常的体外和体内效应功能。因此,Styk1 的表达是 NK 细胞、ILC1 和 NK1.1 T 细胞的特征,但对其发育和免疫功能是可有可无的。