1. Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children
- Author
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Zhenguang Zhang, Iain R. L. Kean, Lisa M. Dratva, John A. Clark, Eleni Syrimi, Naeem Khan, Esther Daubney, Deborah White, Lauran O’Neill, Catherine Chisholm, Caroline Payne, Sarah Benkenstein, Klaudia Kupiec, Rachel Galassini, Victoria Wright, Helen Winmill, Ceri Robbins, Katherine Brown, Padmanabhan Ramnarayan, Barnaby Scholefield, Mark Peters, Nigel Klein, Hugh Montgomery, Kerstin B. Meyer, Sarah A. Teichmann, Clare Bryant, Graham Taylor, and Nazima Pathan
- Subjects
Science - Abstract
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.
- Published
- 2024
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