β-hydroxybutyrylation and O-GlcNAc modifications of STAT1 modulate antiviral defense in aging.

IF 21.8 1区医学 Q1 IMMUNOLOGY

Cellular &Molecular Immunology Pub Date : 2025-02-20 DOI:10.1038/s41423-025-01266-x

Yibo Zuo, Qin Wang, Wanying Tian, Zhijin Zheng, Wei He, Renxia Zhang, Qian Zhao, Ying Miao, Yukang Yuan, Jun Wang, Hui Zheng

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引用次数: 0

Abstract

Aging changes the protein activity status to affect the body's functions. However, how aging regulates protein posttranslational modifications (PTMs) to modulate the antiviral defense ability of the body remains unclear. Here, we found that aging promotes STAT1 β-hydroxybutyrylation (Kbhb) at Lys592, which inhibits the interaction between STAT1 and type-I interferon (IFN-I) receptor 2 (IFNAR2), thereby attenuating IFN-I-mediated antiviral defense activity. Additionally, we discovered that a small molecule from a plant source, hydroxy camptothecine, can effectively reduce the level of STAT1 Kbhb, thus increasing antiviral defense ability in vivo. Further studies revealed that STAT1 O-GlcNAc modifications at Thr699 block CBP-induced STAT1 Kbhb. Importantly, fructose can improve IFN-I antiviral defense activity by orchestrating STAT1 O-GlcNAc and Kbhb modifications. This study reveals the significance of the switch between STAT1 Kbhb and O-GlcNAc modifications in regulating IFN-I antiviral immunity during aging and provides potential strategies to improve the body's antiviral defense ability in elderly individuals.

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来源期刊

Cellular &Molecular Immunology 医学-免疫学

CiteScore

31.20

自引率

1.20%

发文量

903

审稿时长

1 months

期刊介绍： Cellular & Molecular Immunology, a monthly journal from the Chinese Society of Immunology and the University of Science and Technology of China, serves as a comprehensive platform covering both basic immunology research and clinical applications. The journal publishes a variety of article types, including Articles, Review Articles, Mini Reviews, and Short Communications, focusing on diverse aspects of cellular and molecular immunology.