Research Department Virus Immunology, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Institute for Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Front Immunol. 2018 Dec 19;9:3020. doi: 10.3389/fimmu.2018.03020. eCollection 2018.
NK cells expressing self-inhibitory receptors display increased functionality compared to NK cells lacking those receptors. The acquisition of functional competence in these particular NK-cell subsets is termed education. Little is known about the underlying mechanisms that lead to the functional differences between educated and uneducated NK cells. An increasing number of studies suggest that cellular metabolism is a determinant of immune cell functions. Thus, alterations in cellular metabolic pathways may play a role in the process of NK-cell education. Here, we compared the glycolytic profile of educated and uneducated primary human NK cells. KIR-educated NK cells showed significantly increased expression levels of the glucose transporter Glut1 in comparison to NKG2A-educated or uneducated NK cells with and without exposure to target cells. Subsequently, the metabolic profile of NK-cell subsets was determined using a Seahorse XF Analyzer. Educated NK cells displayed significantly higher rates of cellular glycolysis than uneducated NK cells even in a resting state. Our results indicate that educated and uneducated NK cells reside in different metabolic states prior to activation. These differences in the ability to utilize glucose may represent an underlying mechanism for the superior functionality of educated NK cells expressing self-inhibitory receptors.
表达自身抑制性受体的 NK 细胞与缺乏这些受体的 NK 细胞相比，表现出更高的功能。这些特定 NK 细胞亚群获得功能能力的过程被称为教育。对于导致受过教育和未受过教育的 NK 细胞之间功能差异的潜在机制知之甚少。越来越多的研究表明，细胞代谢是免疫细胞功能的决定因素。因此，细胞代谢途径的改变可能在 NK 细胞教育过程中发挥作用。在这里，我们比较了受过教育和未受过教育的原代人 NK 细胞的糖酵解谱。与未经教育或未经教育的 NK 细胞相比，KIR 教育的 NK 细胞在与靶细胞接触前后，葡萄糖转运蛋白 Glut1 的表达水平显著增加。随后，使用 Seahorse XF 分析仪确定 NK 细胞亚群的代谢谱。即使在静止状态下，受过教育的 NK 细胞的细胞糖酵解率也明显高于未受过教育的 NK 细胞。我们的结果表明，在激活之前，受过教育和未受过教育的 NK 细胞处于不同的代谢状态。这种利用葡萄糖的能力差异可能代表表达自身抑制性受体的受过教育的 NK 细胞具有优越功能的潜在机制。
