China Innovation Center of Roche (CICoR), Roche R&D Center (China) Ltd, Shanghai, China.
PLoS One. 2022 Oct 21;17(10):e0276460. doi: 10.1371/journal.pone.0276460. eCollection 2022.
Excessive neutrophil infiltration and dysfunction contribute to the progression and severity of hyper-inflammatory syndrome, such as in severe COVID19. In the current study, we re-analysed published scRNA-seq datasets of mouse and human neutrophils to classify and compare the transcriptional regulatory networks underlying neutrophil differentiation and inflammatory responses. Distinct sets of TF modules regulate neutrophil maturation, function, and inflammatory responses under the steady state and inflammatory conditions. In COVID19 patients, neutrophil activation was associated with the selective activation of inflammation-specific TF modules. SARS-CoV-2 RNA-positive neutrophils showed a higher expression of type I interferon response TF IRF7. Furthermore, IRF7 expression was abundant in neutrophils from severe patients in progression stage. Neutrophil-mediated inflammatory responses positively correlate with the expressional level of IRF7. Based on these results, we suggest that differential activation of activation-related TFs, such as IRF7 mediate neutrophil inflammatory responses during inflammation.
中性粒细胞过度浸润和功能障碍导致过度炎症综合征的进展和严重程度增加，例如在严重的 COVID-19 中。在本研究中，我们重新分析了已发表的小鼠和人类中性粒细胞的 scRNA-seq 数据集，以分类和比较稳态和炎症条件下中性粒细胞分化和炎症反应的转录调控网络。在稳态和炎症条件下，不同的 TF 模块集调节中性粒细胞的成熟、功能和炎症反应。在 COVID-19 患者中，中性粒细胞的激活与炎症特异性 TF 模块的选择性激活有关。SARS-CoV-2 RNA 阳性的中性粒细胞表现出更高的 I 型干扰素反应 TF IRF7 的表达。此外，进展期严重患者的中性粒细胞中 IRF7 的表达丰富。中性粒细胞介导的炎症反应与 IRF7 的表达水平呈正相关。基于这些结果，我们认为，IRF7 等与激活相关的 TF 的差异激活介导了炎症期间的中性粒细胞炎症反应。
