Departments of Paediatrics, University of Cambridge, Cambridge, UK.
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.
Nat Commun. 2024 May 18;15(1):4227. doi: 10.1038/s41467-024-48699-y.
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.
儿童多系统炎症综合征是一种 SARS-CoV-2 感染后综合征，与 T 细胞受体 Vβ21.3+ T 细胞亚群的扩增有关。在这里，我们应用多单细胞组学比较了患有急性呼吸道 COVID-19 的儿童和患有非 SARS-CoV-2 感染的儿童的炎症过程。在这里，我们表明，在儿童多系统炎症综合征（MIS-C）中，自然杀伤细胞和单核细胞群体表现出高表达 CD95（Fas）和白细胞介素 18 受体。此外，TCR Vβ21.3+ CD4+ T 细胞表现出向 T 辅助细胞 1、17 和调节性 T 细胞的偏分化，共刺激受体 ICOS、CD28 和白细胞介素 18 受体的表达增加。我们没有观察到 NLRP3 炎性体途径过度激活的功能证据，尽管 MIS-C 单核细胞显示出活性 caspase 8 的升高。这与单细胞 RNA 测序分析中 CD16-NK 细胞中升高的 IL18 mRNA 表达相结合，表明白细胞介素 18 和 CD95 信号可能通过激活的单核细胞和 CD16-NK 细胞中白细胞介素 18 的产生，触发 MIS-C 中 TCR Vβ21.3+ T 细胞的激活。
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