tetano
Editor, Senior Moderator
Nat Commun
. 2025 Dec 14.
doi: 10.1038/s41467-025-67540-8. Online ahead of print. Aiolos restricts the generation of antigen-inexperienced, virtual memory CD8[SUP]+[/SUP] T cells in mice
Srijana Pokhrel[SUP] 1 [/SUP], Gayathri Dileepan[SUP] 1 2 3 [/SUP], Melissa R Leonard[SUP] 1 4 [/SUP], Robert T Warren[SUP] 1 [/SUP], Mariam Salem[SUP] 1 5 [/SUP], Allison J Yacapraro[SUP] 1 6 [/SUP], Qiaoke Gong[SUP] 1 [/SUP], Devin M Jones[SUP] 1 3 [/SUP], Jasmine A Tuazon[SUP] 1 2 [/SUP], Kaitlin A Read[SUP] 1 3 7 [/SUP], Jacob S Yount[SUP] 1 8 [/SUP], Gang Xin[SUP] 1 9 [/SUP], Adriana Forero[SUP] 1 8 [/SUP], Hazem E Ghoneim[SUP] 1 9 [/SUP], Patrick L Collins[SUP] 1 9 [/SUP], Emily A Hemann[SUP] 1 8 [/SUP], Kenneth J Oestreich[SUP] 10 11 12 [/SUP]
Affiliations
CD8[SUP]+[/SUP] virtual memory T (T[SUB]VM[/SUB]) cells rapidly respond to infection via antigen-independent bystander effector functions. While it is recognized that T[SUB]VM[/SUB] cells arise independently of foreign antigen encounter, the mechanisms governing their development are not fully understood. Here, we identify the Ikaros transcription factor Aiolos as a negative regulator of T[SUB]VM[/SUB] cell programming. We observe enhanced frequencies and numbers of T[SUB]VM[/SUB] in the spleen, liver, and blood of unchallenged Aiolos-deficient (Ikzf3[SUP]-/-[/SUP]) mice and in the lungs 1-day post-infection with influenza A virus (IAV). Furthermore, Ikzf3[SUP]-/-[/SUP] T[SUB]VM[/SUB] cells produce elevated IFN-γ and granzyme B in response to cytokine stimulation. Importantly, Aiolos-deficient mice control IAV more rapidly and exhibit reduced morbidity, indicating enhanced T[SUB]VM[/SUB] cell functionality. Mechanistically, Aiolos represses the expression of the transcription factor Eomes and the IL-15R subunit CD122, known positive regulators of T[SUB]VM[/SUB] gene program. Collectively, these findings establish Aiolos as a molecular repressor of T[SUB]VM[/SUB] programming and responses.
. 2025 Dec 14.
doi: 10.1038/s41467-025-67540-8. Online ahead of print. Aiolos restricts the generation of antigen-inexperienced, virtual memory CD8[SUP]+[/SUP] T cells in mice
Srijana Pokhrel[SUP] 1 [/SUP], Gayathri Dileepan[SUP] 1 2 3 [/SUP], Melissa R Leonard[SUP] 1 4 [/SUP], Robert T Warren[SUP] 1 [/SUP], Mariam Salem[SUP] 1 5 [/SUP], Allison J Yacapraro[SUP] 1 6 [/SUP], Qiaoke Gong[SUP] 1 [/SUP], Devin M Jones[SUP] 1 3 [/SUP], Jasmine A Tuazon[SUP] 1 2 [/SUP], Kaitlin A Read[SUP] 1 3 7 [/SUP], Jacob S Yount[SUP] 1 8 [/SUP], Gang Xin[SUP] 1 9 [/SUP], Adriana Forero[SUP] 1 8 [/SUP], Hazem E Ghoneim[SUP] 1 9 [/SUP], Patrick L Collins[SUP] 1 9 [/SUP], Emily A Hemann[SUP] 1 8 [/SUP], Kenneth J Oestreich[SUP] 10 11 12 [/SUP]
Affiliations
- PMID: 41392082
- DOI: 10.1038/s41467-025-67540-8
CD8[SUP]+[/SUP] virtual memory T (T[SUB]VM[/SUB]) cells rapidly respond to infection via antigen-independent bystander effector functions. While it is recognized that T[SUB]VM[/SUB] cells arise independently of foreign antigen encounter, the mechanisms governing their development are not fully understood. Here, we identify the Ikaros transcription factor Aiolos as a negative regulator of T[SUB]VM[/SUB] cell programming. We observe enhanced frequencies and numbers of T[SUB]VM[/SUB] in the spleen, liver, and blood of unchallenged Aiolos-deficient (Ikzf3[SUP]-/-[/SUP]) mice and in the lungs 1-day post-infection with influenza A virus (IAV). Furthermore, Ikzf3[SUP]-/-[/SUP] T[SUB]VM[/SUB] cells produce elevated IFN-γ and granzyme B in response to cytokine stimulation. Importantly, Aiolos-deficient mice control IAV more rapidly and exhibit reduced morbidity, indicating enhanced T[SUB]VM[/SUB] cell functionality. Mechanistically, Aiolos represses the expression of the transcription factor Eomes and the IL-15R subunit CD122, known positive regulators of T[SUB]VM[/SUB] gene program. Collectively, these findings establish Aiolos as a molecular repressor of T[SUB]VM[/SUB] programming and responses.