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- Title
Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children.
- Authors
Zhang, Zhenguang; Kean, Iain R. L.; Dratva, Lisa M.; Clark, John A.; Syrimi, Eleni; Khan, Naeem; Daubney, Esther; White, Deborah; O'Neill, Lauran; Chisholm, Catherine; Payne, Caroline; Benkenstein, Sarah; Kupiec, Klaudia; Galassini, Rachel; Wright, Victoria; Winmill, Helen; Robbins, Ceri; Brown, Katherine; Ramnarayan, Padmanabhan; Scholefield, Barnaby
- 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. Multi-Inflammatory Syndrome in Children (MIS-C) is a severe post-infectious presentation related to SARS-CoV-2 infection. Here authors used multi-omics approaches to characterise MIS-C cases and found increased CD95 and IL-18 signalling accompanying the expansion of TCR Vβ 21.3+ T cells.
- Subjects
T cells; T cell receptors; MULTISYSTEM inflammatory syndrome in children; SYNDROMES in children; INTERLEUKIN receptors; KILLER cells; REGULATORY T cells; KILLER cell receptors
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-48699-y