PDF(Pubmed)
Abstract：
Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vβ21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vβ21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vβ21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.
摘要：
儿童多系统炎症综合征是与T细胞受体Vβ21.3T细胞亚群扩增相关的SARS-CoV-2感染后表现。在这里，我们应用多单细胞组学比较急性呼吸道感染COVID-19儿童和非SARS-CoV-2感染儿童的炎症过程。在这里，我们表明，在儿童多炎症综合征(MIS-C)中，自然杀伤细胞和单核细胞群显示CD95(Fas)和Interleuking18受体表达升高.此外,TCRVβ21.3+CD4+T细胞向T辅助细胞1、17和调节性T细胞倾斜分化，随着共刺激受体ICOS的表达增加，CD28和白介素18受体。我们没有观察到NLRP3炎性体通路过度激活的功能证据，尽管MIS-C单核细胞显示活性半胱天冬酶8升高。这个,在单细胞RNA测序分析中，CD16-NK细胞中IL18mRNA表达升高，提示白细胞介素18和CD95信号传导可能触发MIS-C中TCRVβ21.3+T细胞的激活，由激活的单核细胞和CD16-自然杀伤细胞产生的IL-18增加驱动。
