@article{discovery10192583,
       publisher = {Springer Science and Business Media LLC},
           title = {Enhanced CD95 and interleukin 18 signalling
accompany T cell receptor V{\ensuremath{\beta}}21.3+
activation in multi-inflammatory syndrome
in children},
            year = {2024},
         journal = {Nature Communications},
          volume = {15},
           month = {May},
            note = {{\copyright} 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 V{\ensuremath{\beta}}21.3+ 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 V{\ensuremath{\beta}}21.3+ 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 V{\ensuremath{\beta}}21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.},
            issn = {2041-1723},
          author = {Zhang, Zhenguang and Kean, Iain RL and Dratva, Lisa M and Clark, John A and Syrimi, Eleni and Khan, Naeem and Daubney, Esther and White, Deborah and O'Neill, Lauran and Chisholm, Catherine and Payne, Caroline and Benkenstein, Sarah and Kupiec, Klaudia and Galassini, Rachel and Wright, Victoria and Winmill, Helen and Robbins, Ceri and Brown, Katherine and Ramnarayan, Padmanabhan and Scholefield, Barnaby and Peters, Mark and Klein, Nigel and Montgomery, Hugh and Meyer, Kerstin B and Teichmann, Sarah A and Bryant, Clare and Taylor, Graham and Pathan, Nazima},
             url = {https://doi.org/10.1038/s41467-024-48699-y},
        keywords = {Adaptive immunity, Inflammatory diseases, SARS-CoV-2, 
Viral infection}
}