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Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children

Author

Listed:
  • Zhenguang Zhang

    (University of Cambridge)

  • Iain R. L. Kean

    (University of Cambridge)

  • Lisa M. Dratva

    (Wellcome Genome Campus)

  • John A. Clark

    (University of Cambridge)

  • Eleni Syrimi

    (University of Birmingham)

  • Naeem Khan

    (University of Birmingham)

  • Esther Daubney

    (Addenbrookes Hospital)

  • Deborah White

    (Addenbrookes Hospital)

  • Lauran O’Neill

    (Great Ormond Street Hospital)

  • Catherine Chisholm

    (Great Ormond Street Hospital)

  • Caroline Payne

    (Great Ormond Street Hospital)

  • Sarah Benkenstein

    (Great Ormond Street Hospital)

  • Klaudia Kupiec

    (Great Ormond Street Hospital)

  • Rachel Galassini

    (Imperial College London)

  • Victoria Wright

    (Imperial College London)

  • Helen Winmill

    (Birmingham Children’s Hospital)

  • Ceri Robbins

    (Birmingham Children’s Hospital)

  • Katherine Brown

    (Great Ormond Street Hospital)

  • Padmanabhan Ramnarayan

    (Imperial College London)

  • Barnaby Scholefield

    (Birmingham Children’s Hospital
    University of Birmingham)

  • Mark Peters

    (Great Ormond Street Hospital
    University College London)

  • Nigel Klein

    (Great Ormond Street Hospital
    University College London)

  • Hugh Montgomery

    (University College London)

  • Kerstin B. Meyer

    (Wellcome Genome Campus)

  • Sarah A. Teichmann

    (Wellcome Genome Campus
    Department of Physics University of Cambridge)

  • Clare Bryant

    (University of Cambridge)

  • Graham Taylor

    (University of Birmingham)

  • Nazima Pathan

    (University of Cambridge
    Addenbrookes Hospital)

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.

Suggested Citation

  • 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 Benkenste, 2024. "Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48699-y
    DOI: 10.1038/s41467-024-48699-y
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    References listed on IDEAS

    as
    1. Zhen Wang & Lijian Xie & Guohui Ding & Sirui Song & Liqin Chen & Guang Li & Min Xia & Dingding Han & Yue Zheng & Jia Liu & Tingting Xiao & Hong Zhang & Yujuan Huang & Yixue Li & Min Huang, 2021. "Single-cell RNA sequencing of peripheral blood mononuclear cells from acute Kawasaki disease patients," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
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