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ICOS-ICOSL通路增强COVID-19孕妇中NKT样细胞的抗病毒功能。

ICOS-ICOSL pathway enhances NKT-like cell antiviral function in pregnant women with COVID-19.

作者信息

Zong Lu, Zheng Yuanling, Yu Xiaojing, Dai Xiaoran, Huang Ruoyu, Yan Guoxiu, Xu Yuanhong, Zheng Meijuan

机构信息

Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Anhui Medical University, Hefei, Anhui, China.

出版信息

Int J Med Sci. 2024 Jul 16;21(10):1890-1902. doi: 10.7150/ijms.95952. eCollection 2024.

DOI:10.7150/ijms.95952
PMID:39113896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11302565/
Abstract

The immune response initiated by SARS-CoV-2 infection in pregnancy is poorly elucidated. We aimed to access and compare the antiviral cellular responses and lymphocytes activation between healthy pregnancies and pregnant women infected with SARS-CoV-2. We detected the immunological changes of lymphocytes in peripheral blood of healthy non-pregnant women, non-pregnant women with COVID-19, healthy pregnant women, pregnant women with COVID-19 and convalescent group by flow cytometry. blockade was used to identify NKT-like cell activation through ICOS-ICOSL pathway. We found that CD3CD56 NKT-like cells decreased significantly in COVID-19 positive pregnant women compared to healthy pregnant women. NKT-like cells of pregnant women expressed higher level of activating receptors CD69 and NKp46 after SARS-CoV-2 infection. Particularly, they also increased the expression of the co-stimulatory molecule ICOS. NKT-like cells of pregnant women with COVID-19 up-regulated the expression of IFN-γ, CD107a and Ki67. Meanwhile, we found that ICOSL expression was significantly increased on pDCs in pregnant women with COVID-19. Blocking ICOS significantly decreased the antiviral activity of NKT-like cells in COVID-19 positive pregnant women, suggesting that ICOS-ICOSL may play an important role in the virus clearance by NKT-like cells. During SARS-CoV-2 infection, NKT-like cells of pregnant women activated through ICOS-ICOSL pathway and played an important role in the antiviral response.

摘要

孕期由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染引发的免疫反应尚不清楚。我们旨在评估和比较健康孕妇与感染SARS-CoV-2的孕妇之间的抗病毒细胞反应和淋巴细胞激活情况。我们通过流式细胞术检测了健康非孕妇、感染新型冠状病毒肺炎(COVID-19)的非孕妇、健康孕妇、感染COVID-19的孕妇以及恢复期组外周血淋巴细胞的免疫变化。采用阻断法通过诱导性共刺激分子(ICOS)-ICOS配体(ICOSL)途径鉴定自然杀伤T(NKT)样细胞的激活情况。我们发现,与健康孕妇相比,COVID-19阳性孕妇的CD3CD56 NKT样细胞显著减少。SARS-CoV-2感染后,孕妇的NKT样细胞表达更高水平的激活受体CD69和自然杀伤细胞蛋白46(NKp46)。特别是,它们还增加了共刺激分子ICOS的表达。感染COVID-19的孕妇的NKT样细胞上调了γ干扰素(IFN-γ)、CD107a和Ki-67抗原(Ki67)的表达。同时,我们发现感染COVID-19的孕妇的浆细胞样树突状细胞(pDCs)上ICOSL的表达显著增加。阻断ICOS可显著降低COVID-19阳性孕妇中NKT样细胞的抗病毒活性,这表明ICOS-ICOSL可能在NKT样细胞清除病毒中起重要作用。在SARS-CoV-2感染期间,孕妇的NKT样细胞通过ICOS-ICOSL途径被激活,并在抗病毒反应中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2dc/11302565/d186c4c124fa/ijmsv21p1890g006.jpg
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