Servicio de Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
Department of Immunology, Ophthalmology and ENT. Complutense University School of Medicine and 12 de Octubre Health Research Institute (imas12), Madrid, Spain.
Sci Rep. 2019 Feb 18;9(1):2211. doi: 10.1038/s41598-019-38647-y.
Aurora A is a serine/threonine kinase whose role in cell cycle progression and tumour generation has been widely studied. Recent work has revealed an unexpected function for Aurora A during CD4 T cell activation and, also, in graft versus host disease development. However, it remains unknown whether Aurora A is involved in CD8 T cell effector function and in cytotoxic T lymphocyte-mediated antiviral response. Here, we show that Aurora A chemical inhibition leads to an impairment of both the peptide-specific cytotoxicity and the degranulation activity of CD8 T cells. This finding was similarly proven for both mice and human CD8 CTL activity. As a result of Aurora A blockade, we detected a reduction in the expression induced by T cell activation of genes classically related to the effector function of cytotoxic T lymphocytes such as granzyme B or perforin1. Finally, we have found that Aurora A is necessary for CD8 T cell-mediated antiviral response, in an in vivo model of vaccinia virus infection. Thus, we can conclude that Aurora A activity is, indeed, needed for the proper effector function of cytotoxic T lymphocytes and for their activity against viral threats.
极光 A 是一种丝氨酸/苏氨酸激酶，其在细胞周期进程和肿瘤发生中的作用已被广泛研究。最近的工作揭示了极光 A 在 CD4 T 细胞活化过程中的一个意想不到的功能，也揭示了在移植物抗宿主病发展中的作用。然而，目前尚不清楚极光 A 是否参与 CD8 T 细胞效应功能和细胞毒性 T 淋巴细胞介导的抗病毒反应。在这里，我们表明极光 A 的化学抑制导致 CD8 T 细胞的肽特异性细胞毒性和脱颗粒活性受损。这一发现同样适用于小鼠和人类 CD8 CTL 活性。由于极光 A 的阻断，我们检测到由 T 细胞激活诱导的基因的表达减少，这些基因经典地与细胞毒性 T 淋巴细胞的效应功能相关，如颗粒酶 B 或穿孔素 1。最后，我们发现极光 A 在痘苗病毒感染的体内模型中是 CD8 T 细胞介导的抗病毒反应所必需的。因此，我们可以得出结论，极光 A 的活性确实是细胞毒性 T 淋巴细胞发挥适当效应功能和对抗病毒威胁所必需的。
