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eLife

eLife

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Aurora kinase A promotes trained immunity via regulation of endogenous S-adenosylmethionine metabolism

Published:8 September 2025 DOI: 10.7554/eLife.104138 PMID: 40920087
Mengyun Li,?Huan Jin,?Yongxiang Liu,?Zining Wang,?Lin Li,?Tiantian Wang,?Xiaojuan Wang,?Hongxia Zhang,?Bitao Huo,?Tiantian Yu,?Shoujie Wang,?Wei Zhao,?Jinyun Liu,?Peng Huang,?Jun Cui,?Xiaojun Xia

Abstract

Innate immune cells can acquire a memory phenotype, termed trained immunity, but the mechanism underlying the regulation of trained immunity remains largely elusive. Here, we demonstrate that inhibition of Aurora kinase A (AurA) dampens trained immunity induced by β-glucan. ATAC-seq and RNA-seq analysis reveal that AurA inhibition restricts chromatin accessibility of genes associated with inflammatory pathways such as JAK-STAT, TNF, and NF-κB pathways. Specifically, AurA inhibition promotes nuclear localization of FOXO3 and the expression of glycine N-methyltransferase (GNMT), a key enzyme responsible for S-adenosylmethionine (SAM) consumption. Metabolomic analysis confirms a reduction in SAM level upon AurA inhibition. As a result of SAM deficiency, trained mouse macrophages exhibit decreased H3K4me3 and H3K36me3 enrichment on gene regions of Il6 and Tnf. Additionally, the tumor inhibition effect of β-glucan is notably abolished by AurA inhibition. Together, our findings identify an essential role of AurA in regulating trained immunity via a methylation-dependent manner by maintaining endogenous SAM levels through the mTOR-FOXO3-GNMT axis.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Tozasertib 639089-54-6 C23H28N8OS 232 suppliers $11.00-$1840.00
Tozasertib 639089-54-6 C23H28N8OS 232 suppliers $11.00-$1840.00
Tozasertib 639089-54-6 C23H28N8OS 232 suppliers $11.00-$1840.00
Tozasertib 639089-54-6 C23H28N8OS 232 suppliers $11.00-$1840.00
MLN-8237 1028486-01-2 C27H20ClFN4O4 226 suppliers $17.00-$2691.10
MLN-8237 1028486-01-2 C27H20ClFN4O4 226 suppliers $17.00-$2691.10
MLN-8237 1028486-01-2 C27H20ClFN4O4 226 suppliers $17.00-$2691.10
MLN-8237 1028486-01-2 C27H20ClFN4O4 226 suppliers $17.00-$2691.10

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