Circulating Reelin promotes inflammation and modulates disease activity in acute and long COVID-19 cases.
Circulating Reelin promotes inflammation and modulates disease activity in acute and long COVID-19 cases.
复制标题
循环 Reelin 可促进急性和长期 COVID-19 病例的炎症并调节疾病活动。
DOI：
10.3389/fimmu.2023.1185748
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发表时间：
2023
影响因子：
7.3
通讯作者：
Herz, Joachim
中科院分区：
文献类型：
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作者：
Calvier, Laurent;Drelich, Aleksandra;Hsu, Jason;Tseng, Chien-Te;Mina, Yair;Nath, Avindra;Kounnas, Maria Z.;Herz, Joachim
关键词：
血栓栓塞并发症和过度炎症在严重的COVID-19中很常见，可能导致长期COVID。在非COVID研究中，我们和其他人证明了循环中的Reelin促进白细胞浸润和血栓形成。因此，我们假设Reelin参与了COVID-19期间的内皮功能障碍和炎症过度。我们发现，Reelin在COVID-19患者中增加，并与疾病活动相关。在重度COVID-19组中，我们观察到了高度炎症状态，这是通过细胞因子（IL-1α、IL-4、IL-6、IL-10和IL-17 A）、趋化因子（IP-10和MIP-1β）和粘附标志物（E-选择素和ICAM-1）浓度升高来判断的。Reelin水平与IL-1α、IL-4、IP-10、MIP-1β和ICAM-1相关，表明Reelin在COVID-19进展中的特定作用。此外，Reelin和上述所有炎症标志物在长COVID队列中恢复正常，表明炎症过度状态得到解决。最后，我们在感染SARS-CoV-2的hACE 2转基因小鼠中测试了抗Reelin抗体CR-50对Reelin的抑制作用。CR-50预防性治疗降低了该模型中的死亡率和疾病严重程度。这些结果证明了Reelin在COVID-19中的直接促炎功能，并将其确定为药物靶标。这项工作开启了严重SARS-CoV-2感染以及自身炎症性疾病的转化临床应用。
Thromboembolic complications and excessive inflammation are frequent in severe COVID-19, potentially leading to long COVID. In non-COVID studies, we and others demonstrated that circulating Reelin promotes leukocyte infiltration and thrombosis. Thus, we hypothesized that Reelin participates in endothelial dysfunction and hyperinflammation during COVID-19. We showed that Reelin was increased in COVID-19 patients and correlated with the disease activity. In the severe COVID-19 group, we observed a hyperinflammatory state, as judged by increased concentration of cytokines (IL-1α, IL-4, IL-6, IL-10 and IL-17A), chemokines (IP-10 and MIP-1β), and adhesion markers (E-selectin and ICAM-1). Reelin level was correlated with IL-1α, IL-4, IP-10, MIP-1β, and ICAM-1, suggesting a specific role for Reelin in COVID-19 progression. Furthermore, Reelin and all of the inflammatory markers aforementioned returned to normal in a long COVID cohort, showing that the hyperinflammatory state was resolved. Finally, we tested Reelin inhibition with the anti-Reelin antibody CR-50 in hACE2 transgenic mice infected with SARS-CoV-2. CR-50 prophylactic treatment decreased mortality and disease severity in this model. These results demonstrate a direct proinflammatory function for Reelin in COVID-19 and identify it as a drug target. This work opens translational clinical applications in severe SARS-CoV-2 infection and beyond in auto-inflammatory diseases.
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影响因子：
8.8
作者：
通讯作者：
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DOI：
10.1016/j.jacbts.2021.09.011
发表时间：
2022-03
期刊：
JACC. Basic to translational science
影响因子：
--
作者：
Calvier L;Herz J;Hansmann G
通讯作者：
Hansmann G
影响因子：
5.3
作者：
DArcangelo, G;Nakajima, K;Curran, T
通讯作者：
Curran, T
影响因子：
82.9
作者：
Blomberg B;Mohn KG;Brokstad KA;Zhou F;Linchausen DW;Hansen BA;Lartey S;Onyango TB;Kuwelker K;Sævik M;Bartsch H;Tøndel C;Kittang BR;Bergen COVID-19 Research Group;Cox RJ;Langeland N
通讯作者：
Langeland N
影响因子：
3.6
作者：
通讯作者：
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