tetano
Editor, Senior Moderator
Nat Commun
. 2025 Nov 24;16(1):10344.
doi: 10.1038/s41467-025-65262-5. High expression of interleukin-18 receptor alpha correlates with severe respiratory viral disease and defines T cells with reduced cytotoxic signatures
Aira F Cabug[SUP] 1 [/SUP], Jeremy Chase Crawford[SUP] 2 3 [/SUP], Hayley A McQuilten[SUP] 1 [/SUP], Isabelle J H Foo[SUP] 1 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Deborah Gebregzabher[SUP] 1 [/SUP], Robert C Mettelman[SUP] 2 [/SUP], Tanya Novak[SUP] 4 [/SUP], Janet Chou[SUP] 5 [/SUP], Louise C Rowntree[SUP] 1 [/SUP], Ruth R Hagen[SUP] 1 [/SUP], Abby J Thomson[SUP] 1 [/SUP], Genevieve E Martin[SUP] 1 6 [/SUP], Brad Gilbertson[SUP] 1 [/SUP], Michael Nt Souter[SUP] 1 [/SUP], Fiona James[SUP] 6 [/SUP], Emma Goodall[SUP] 6 [/SUP], Simone Rizzetto[SUP] 7 [/SUP], Tim Flerlage[SUP] 8 [/SUP], Xiaoxiao Jia[SUP] 1 [/SUP], Lee-Ann Van de Velde[SUP] 2 [/SUP], So Young Chang[SUP] 1 [/SUP], Fabio Luciani[SUP] 7 [/SUP], Ryan S Thwaites[SUP] 9 [/SUP], Jason A Trubiano[SUP] 10 11 12 13 [/SUP], Tom C Kotsimbos[SUP] 14 15 [/SUP], Allen C Cheng[SUP] 16 17 [/SUP], Adrienne G Randolph[SUP] 4 18 [/SUP], Paul G Thomas[SUP] 2 18 [/SUP], Jianqing Xu[SUP] 19 [/SUP], Zhongfang Wang[SUP] 1 20 [/SUP], Thi H O Nguyen[SUP] #[/SUP][SUP] 1 [/SUP], Brendon Y Chua[SUP] #[/SUP][SUP] 1 [/SUP], Lukasz Kedzierski[SUP] #[/SUP][SUP] 1 [/SUP], Katherine Kedzierska[SUP] #[/SUP][SUP] 21 22 [/SUP]
Affiliations
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.
. 2025 Nov 24;16(1):10344.
doi: 10.1038/s41467-025-65262-5. High expression of interleukin-18 receptor alpha correlates with severe respiratory viral disease and defines T cells with reduced cytotoxic signatures
Aira F Cabug[SUP] 1 [/SUP], Jeremy Chase Crawford[SUP] 2 3 [/SUP], Hayley A McQuilten[SUP] 1 [/SUP], Isabelle J H Foo[SUP] 1 [/SUP], Lilith F Allen[SUP] 1 [/SUP], Deborah Gebregzabher[SUP] 1 [/SUP], Robert C Mettelman[SUP] 2 [/SUP], Tanya Novak[SUP] 4 [/SUP], Janet Chou[SUP] 5 [/SUP], Louise C Rowntree[SUP] 1 [/SUP], Ruth R Hagen[SUP] 1 [/SUP], Abby J Thomson[SUP] 1 [/SUP], Genevieve E Martin[SUP] 1 6 [/SUP], Brad Gilbertson[SUP] 1 [/SUP], Michael Nt Souter[SUP] 1 [/SUP], Fiona James[SUP] 6 [/SUP], Emma Goodall[SUP] 6 [/SUP], Simone Rizzetto[SUP] 7 [/SUP], Tim Flerlage[SUP] 8 [/SUP], Xiaoxiao Jia[SUP] 1 [/SUP], Lee-Ann Van de Velde[SUP] 2 [/SUP], So Young Chang[SUP] 1 [/SUP], Fabio Luciani[SUP] 7 [/SUP], Ryan S Thwaites[SUP] 9 [/SUP], Jason A Trubiano[SUP] 10 11 12 13 [/SUP], Tom C Kotsimbos[SUP] 14 15 [/SUP], Allen C Cheng[SUP] 16 17 [/SUP], Adrienne G Randolph[SUP] 4 18 [/SUP], Paul G Thomas[SUP] 2 18 [/SUP], Jianqing Xu[SUP] 19 [/SUP], Zhongfang Wang[SUP] 1 20 [/SUP], Thi H O Nguyen[SUP] #[/SUP][SUP] 1 [/SUP], Brendon Y Chua[SUP] #[/SUP][SUP] 1 [/SUP], Lukasz Kedzierski[SUP] #[/SUP][SUP] 1 [/SUP], Katherine Kedzierska[SUP] #[/SUP][SUP] 21 22 [/SUP]
Affiliations
- PMID: 41285788
- DOI: 10.1038/s41467-025-65262-5
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.