The immunological role of B7-H4 in pregnant women with Sars-Cov2 infection
The immunological role of B7-H4 in pregnant women with Sars-Cov2 infection
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DOI：
10.1111/aji.13626
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发表时间：
2022-09-28
影响因子：
3.6
通讯作者：
Iannaccone, Antonella
中科院分区：
文献类型：
--
作者：
Duan, Liyan;Reisch, Beatrix;Iannaccone, Antonella
问题T细胞是抗击2019年冠状病毒疾病的关键参与者(新冠肺炎)。检验点分子B7-H4是B7家族的一员，通过抑制核因子-kb的表达来抑制T细胞的激活和增殖。我们的目的是阐明可溶性B7-H4(SB7-H4)和B7-H4在孕妇急性SARS-Cov2感染中的免疫学作用。方法采用酶联免疫吸附试验检测SB7-H4和细胞因子的表达水平。用定量聚合酶链式反应分析B7-H4和细胞因子的基因表达，用免疫印迹和免疫荧光染色检测B7-H4和核因子-kappab(P65)在新冠肺炎感染组和正常对照组胎盘绒毛和蜕膜基底层组织中的表达。结果新冠肺炎感染组胎盘绒毛周边纤维素样坏死明显增加。在SARS-CoV-2感染过程中，母血和脐血中SB7-H4蛋白和IL-6/IL-10升高，白细胞下降。血清SB7-H4水平随SARS-CoV-2感染程度的加重而升高。新冠肺炎感染孕妇蜕膜组织中细胞因子IL-6、IL-18、IL-1β、肿瘤坏死因子-α、B7-H4mRNA和蛋白水平均显著高于正常对照组。新冠肺炎患者胎盘绒毛组织中IL-18和IL-1β的表达显著升高，而核因子-kappab(P65)的表达降低。结论免疫标志物SB7-H4的表达与妊娠合并新冠肺炎病的严重程度有关。SB7-H4和B7-H4可用于监测孕期新冠肺炎感染的进展情况，并可用于评估母亲的免疫状态。
Problem T-cells are key players in fighting the coronavirus disease 2019 (COVID-19). The checkpoint molecule B7-H4, a member of the B7 family, can inhibit T-cell activation and proliferation by inhibiting NF-kb expression. We aimed to elucidate the immunological role of soluble B7-H4 (sB7-H4) and B7-H4 in pregnant women suffered from an acute Sars-Cov2 infection. Methods Expression levels of sB7-H4 and cytokines were detected by enzyme linked immunosorbent assay. B7-H4 and cytokines mRNA expression was analyzed by qPCR, and B7-H4 and NF-kappa b (p65) protein levels were investigated by western blot and immunofluorescence staining in placenta chorionic villous and decidual basalis tissues of COVID-19 affected women and healthy controls. Results Fibrinoid necrosis in the periphery of placental villi was increased in the COVID-19-affected patients. sB7-H4 protein in maternal and cord blood serum and IL-6/IL-10 were increased while leukocytes were decreased during SARS-CoV-2 infection. Serum sB7-H4 level was increased according to the severity of SARS-Cov-2 infection. Cytokines (IL-6, IL-18, IL-1 beta, TNF-alpha), B7-H4 mRNA and protein in the decidual basalis tissues of COVID-19-infected pregnant women were significantly increased compared to healthy controls. IL-18 and IL-1 beta were significantly increased in the placenta chorionic villous samples of COVID-19 affected patients, while NF-kappa b (p65) expression was decreased. Conclusions The expression of the immunological marker sB7-H4 correlated with the severity of COVID-19 disease in pregnant women. sB7-H4 and B7-H4 can be used to monitor the progression of COVID-19 infection during pregnancy, and for evaluating of the maternal immune status.