TY  - JOUR
N1  - © 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/
TI  - Enhanced CD95 and interleukin 18 signalling
accompany T cell receptor V?21.3+
activation in multi-inflammatory syndrome
in children
AV  - public
VL  - 15
Y1  - 2024/05/18/
JF  - Nature Communications
A1  - Zhang, Zhenguang
A1  - Kean, Iain RL
A1  - Dratva, Lisa M
A1  - Clark, John A
A1  - Syrimi, Eleni
A1  - Khan, Naeem
A1  - Daubney, Esther
A1  - White, Deborah
A1  - O'Neill, Lauran
A1  - Chisholm, Catherine
A1  - Payne, Caroline
A1  - Benkenstein, Sarah
A1  - Kupiec, Klaudia
A1  - Galassini, Rachel
A1  - Wright, Victoria
A1  - Winmill, Helen
A1  - Robbins, Ceri
A1  - Brown, Katherine
A1  - Ramnarayan, Padmanabhan
A1  - Scholefield, Barnaby
A1  - Peters, Mark
A1  - Klein, Nigel
A1  - Montgomery, Hugh
A1  - Meyer, Kerstin B
A1  - Teichmann, Sarah A
A1  - Bryant, Clare
A1  - Taylor, Graham
A1  - Pathan, Nazima
KW  - Adaptive immunity
KW  -  Inflammatory diseases
KW  -  SARS-CoV-2
KW  -  
Viral infection
N2  - Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor V?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?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?21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.
ID  - discovery10192583
UR  - https://doi.org/10.1038/s41467-024-48699-y
PB  - Springer Science and Business Media LLC
SN  - 2041-1723
ER  -