eprintid: 10192583 rev_number: 10 eprint_status: archive userid: 699 dir: disk0/10/19/25/83 datestamp: 2024-05-21 08:57:35 lastmod: 2024-10-09 14:49:15 status_changed: 2024-05-21 08:57:35 type: article metadata_visibility: show sword_depositor: 699 creators_name: Zhang, Zhenguang creators_name: Kean, Iain RL creators_name: Dratva, Lisa M creators_name: Clark, John A creators_name: Syrimi, Eleni creators_name: Khan, Naeem creators_name: Daubney, Esther creators_name: White, Deborah creators_name: O'Neill, Lauran creators_name: Chisholm, Catherine creators_name: Payne, Caroline creators_name: Benkenstein, Sarah creators_name: Kupiec, Klaudia creators_name: Galassini, Rachel creators_name: Wright, Victoria creators_name: Winmill, Helen creators_name: Robbins, Ceri creators_name: Brown, Katherine creators_name: Ramnarayan, Padmanabhan creators_name: Scholefield, Barnaby creators_name: Peters, Mark creators_name: Klein, Nigel creators_name: Montgomery, Hugh creators_name: Meyer, Kerstin B creators_name: Teichmann, Sarah A creators_name: Bryant, Clare creators_name: Taylor, Graham creators_name: Pathan, Nazima title: Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children ispublished: pub subjects: GOSH divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: D13 divisions: G24 divisions: G94 keywords: Adaptive immunity, Inflammatory diseases, SARS-CoV-2, Viral infection note: © The Author(s), 2024. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ 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. date: 2024-05-18 date_type: published publisher: Springer Science and Business Media LLC official_url: https://doi.org/10.1038/s41467-024-48699-y oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2277040 doi: 10.1038/s41467-024-48699-y medium: Electronic pii: 10.1038/s41467-024-48699-y lyricists_name: Montgomery, Hugh lyricists_name: Peters, Mark lyricists_name: Klein, Nigel lyricists_id: HEMON01 lyricists_id: MJPET74 lyricists_id: NJKLE20 actors_name: Montgomery, Hugh actors_id: HEMON01 actors_role: owner funding_acknowledgements: [Action Medical Research]; [CUH | Addenbrooke’s Charitable Trust, Cambridge University Hospitals] full_text_status: public publication: Nature Communications volume: 15 article_number: 4227 event_location: England issn: 2041-1723 citation: Zhang, Zhenguang; Kean, Iain RL; Dratva, Lisa M; Clark, John A; Syrimi, Eleni; Khan, Naeem; Daubney, Esther; ... Pathan, Nazima; + view all <#> Zhang, Zhenguang; Kean, Iain RL; 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; Peters, Mark; Klein, Nigel; Montgomery, Hugh; Meyer, Kerstin B; Teichmann, Sarah A; Bryant, Clare; Taylor, Graham; Pathan, Nazima; - view fewer <#> (2024) Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children. Nature Communications , 15 , Article 4227. 10.1038/s41467-024-48699-y <https://doi.org/10.1038/s41467-024-48699-y>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10192583/1/Montgomery_Enhanced%20CD95_s41467-024-48699-y.pdf