Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea.
J Allergy Clin Immunol. 2021 Oct;148(4):996-1006.e18. doi: 10.1016/j.jaci.2021.07.022. Epub 2021 Jul 31.
Our understanding of adaptive immune responses in patients with coronavirus disease 2019 (COVID-19) is rapidly evolving, but information on the innate immune responses by natural killer (NK) cells is still insufficient.
We aimed to examine the phenotypic and functional status of NK cells and their changes during the course of mild and severe COVID-19.
We performed RNA sequencing and flow cytometric analysis of NK cells from patients with mild and severe COVID-19 at multiple time points in the course of the disease using cryopreserved PBMCs.
In RNA-sequencing analysis, the NK cells exhibited distinctive features compared with healthy donors, with significant enrichment of proinflammatory cytokine-mediated signaling pathways. Intriguingly, we found that the unconventional CD56CD16 NK-cell population expanded in cryopreserved PBMCs from patients with COVID-19 regardless of disease severity, accompanied by decreased NK-cell cytotoxicity. The NK-cell population was rapidly normalized alongside the disappearance of unconventional CD56CD16 NK cells and the recovery of NK-cell cytotoxicity in patients with mild COVID-19, but this occurred slowly in patients with severe COVID-19.
The current longitudinal study provides a deep understanding of the NK-cell biology in COVID-19.
我们对 2019 冠状病毒病（COVID-19）患者适应性免疫反应的了解正在迅速发展，但关于自然杀伤（NK）细胞固有免疫反应的信息仍然不足。
我们旨在研究 NK 细胞的表型和功能状态及其在轻症和重症 COVID-19 病程中的变化。
我们使用冷冻保存的 PBMC 对轻症和重症 COVID-19 患者在病程中的多个时间点进行了 RNA 测序和 NK 细胞流式细胞分析。
在 RNA 测序分析中，NK 细胞与健康供体相比具有独特的特征，其促炎细胞因子介导的信号通路明显富集。有趣的是，我们发现，无论疾病严重程度如何，COVID-19 患者冷冻保存的 PBMC 中非常规的 CD56CD16 NK 细胞群体都在扩增，同时 NK 细胞的细胞毒性降低。在轻症 COVID-19 患者中，NK 细胞群体随着非常规 CD56CD16 NK 细胞的消失和 NK 细胞细胞毒性的恢复而迅速恢复正常，但在重症 COVID-19 患者中，这一过程较为缓慢。
本纵向研究深入了解了 COVID-19 中的 NK 细胞生物学。
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