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<p>Hyperactivated immunity underpins severe outcomes of respiratory viral infections, yet specific immune perturbations are ill-defined. Our recent findings identified OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. In the same patient cohorts, we now identify the gene encoding IL-18Rα chain (<i>IL18R1</i>), as being highly expressed in life-threatening influenza, COVID-19, RSV and multisystem inflammatory syndrome in children (MIS-C) and demonstrate markedly elevated surface protein IL-18Rα expression on CD8 T cells in these infections. Using a mouse model of severe influenza, we further show that high IL-18Rα expression on effector T cells is associated with increased disease severity. We find that IL-18Rα expression on CD8 T cells is inversely associated with cytotoxicity-related genes, including granzyme A, granzyme B, perforin, Eomes, and KLRG-1. Our study demonstrates that IL-18Rα is associated with severe and fatal respiratory disease outcomes and proposes the use of IL-18Rα as a potential biomarker for severe respiratory viral disease.</p>

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High expression of interleukin-18 receptor alpha correlates with severe respiratory viral disease and defines T cells with reduced cytotoxic signatures

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月24日

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  • Aira F. Cabug,
  • Jeremy Chase Crawford,
  • Hayley A. McQuilten,
  • Isabelle J. H. Foo,
  • Lilith F. Allen,
  • Deborah Gebregzabher,
  • Robert C. Mettelman,
  • Tanya Novak,
  • Janet Chou,
  • Louise C. Rowntree,
  • Ruth R. Hagen,
  • Abby J. Thomson,
  • Genevieve E. Martin,
  • Brad Gilbertson,
  • Michael NT Souter,
  • Fiona James,
  • Emma Goodall,
  • Simone Rizzetto,
  • Tim Flerlage,
  • Xiaoxiao Jia,
  • Lee-Ann Van de Velde,
  • So Young Chang,
  • Fabio Luciani,
  • Ryan S. Thwaites,
  • Jason A. Trubiano,
  • Tom C. Kotsimbos,
  • Allen C. Cheng,
  • Adrienne G. Randolph,
  • Paul G. Thomas,
  • Jianqing Xu,
  • Zhongfang Wang,
  • Thi H. O. Nguyen,
  • Brendon Y. Chua,
  • Lukasz Kedzierski,
  • Katherine Kedzierska

摘要

Hyperactivated immunity underpins severe outcomes of respiratory viral infections, yet specific immune perturbations are ill-defined. Our recent findings identified OLAH (oleoyl-ACP-hydrolase) as a driver of life-threatening viral diseases. In the same patient cohorts, we now identify the gene encoding IL-18Rα chain (IL18R1), as being highly expressed in life-threatening influenza, COVID-19, RSV and multisystem inflammatory syndrome in children (MIS-C) and demonstrate markedly elevated surface protein IL-18Rα expression on CD8 T cells in these infections. Using a mouse model of severe influenza, we further show that high IL-18Rα expression on effector T cells is associated with increased disease severity. We find that IL-18Rα expression on CD8 T cells is inversely associated with cytotoxicity-related genes, including granzyme A, granzyme B, perforin, Eomes, and KLRG-1. Our study demonstrates that IL-18Rα is associated with severe and fatal respiratory disease outcomes and proposes the use of IL-18Rα as a potential biomarker for severe respiratory viral disease.