tetano
Editor, Senior Moderator
Nat Commun
. 2024 May 18;15(1):4227.
doi: 10.1038/s41467-024-48699-y. Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children
Zhenguang Zhang[SUP] 1 [/SUP], Iain R L Kean[SUP] 1 [/SUP], Lisa M Dratva[SUP] 2 [/SUP], John A Clark[SUP] 1 [/SUP], Eleni Syrimi[SUP] 3 [/SUP], Naeem Khan[SUP] 3 [/SUP], Esther Daubney[SUP] 4 [/SUP], Deborah White[SUP] 4 [/SUP], Lauran O'Neill[SUP] 5 [/SUP], Catherine Chisholm[SUP] 5 [/SUP], Caroline Payne[SUP] 5 [/SUP], Sarah Benkenstein[SUP] 5 [/SUP], Klaudia Kupiec[SUP] 5 [/SUP], Rachel Galassini[SUP] 6 [/SUP], Victoria Wright[SUP] 6 [/SUP], Helen Winmill[SUP] 7 [/SUP], Ceri Robbins[SUP] 7 [/SUP], Katherine Brown[SUP] 5 [/SUP], Padmanabhan Ramnarayan[SUP] 6 [/SUP], Barnaby Scholefield[SUP] 7 8 [/SUP], Mark Peters[SUP] 5 9 [/SUP], Nigel Klein[SUP] 5 9 [/SUP], Hugh Montgomery[SUP] 10 [/SUP], Kerstin B Meyer[SUP] 2 [/SUP], Sarah A Teichmann[SUP] 2 11 [/SUP], Clare Bryant[SUP] #[/SUP][SUP] 12 [/SUP], Graham Taylor[SUP] #[/SUP][SUP] 13 [/SUP], Nazima Pathan[SUP] #[/SUP][SUP] 14 15 [/SUP]
Affiliations
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.
. 2024 May 18;15(1):4227.
doi: 10.1038/s41467-024-48699-y. Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children
Zhenguang Zhang[SUP] 1 [/SUP], Iain R L Kean[SUP] 1 [/SUP], Lisa M Dratva[SUP] 2 [/SUP], John A Clark[SUP] 1 [/SUP], Eleni Syrimi[SUP] 3 [/SUP], Naeem Khan[SUP] 3 [/SUP], Esther Daubney[SUP] 4 [/SUP], Deborah White[SUP] 4 [/SUP], Lauran O'Neill[SUP] 5 [/SUP], Catherine Chisholm[SUP] 5 [/SUP], Caroline Payne[SUP] 5 [/SUP], Sarah Benkenstein[SUP] 5 [/SUP], Klaudia Kupiec[SUP] 5 [/SUP], Rachel Galassini[SUP] 6 [/SUP], Victoria Wright[SUP] 6 [/SUP], Helen Winmill[SUP] 7 [/SUP], Ceri Robbins[SUP] 7 [/SUP], Katherine Brown[SUP] 5 [/SUP], Padmanabhan Ramnarayan[SUP] 6 [/SUP], Barnaby Scholefield[SUP] 7 8 [/SUP], Mark Peters[SUP] 5 9 [/SUP], Nigel Klein[SUP] 5 9 [/SUP], Hugh Montgomery[SUP] 10 [/SUP], Kerstin B Meyer[SUP] 2 [/SUP], Sarah A Teichmann[SUP] 2 11 [/SUP], Clare Bryant[SUP] #[/SUP][SUP] 12 [/SUP], Graham Taylor[SUP] #[/SUP][SUP] 13 [/SUP], Nazima Pathan[SUP] #[/SUP][SUP] 14 15 [/SUP]
Affiliations
- PMID: 38762592
- 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.