Bilirubin metabolism in the liver orchestrates antiviral innate immunity in the body.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-03-27 DOI:10.1016/j.celrep.2025.115481

Qian Du, Wei He, Xiangjie Chen, Jin Liu, Mingcheng Guan, Yichang Chen, Meixia Chen, Yukang Yuan, Yibo Zuo, Ying Miao, Qin Wang, Haiyan Zhou, Yanli Liu, Jingting Jiang, Hui Zheng

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引用次数: 0

Abstract

Bilirubin metabolism crucially maintains normal liver function, but whether it contributes to antiviral immunity remains unknown. Here, we reveal that the liver bilirubin metabolic pathway facilitates antiviral innate immunity of the body. We discovered that viral infection upregulates uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression in the liver, which in turn stabilizes IRF3 proteins to promote type I interferon (IFN-I) production. Moreover, we found that serum unconjugated bilirubin (UCB), a unique physiological substrate of UGT1A1, can competitively inhibit the binding of IFN-I to IFN-I receptor 2 (IFNAR2), thus attenuating IFN-I-induced antiviral signaling of the body. Accordingly, effective bilirubin metabolism in the liver promotes antiviral immunity of the body by specifically employing liver UGT1A1-mediated enhancement of IFN-I production and reducing serum bilirubin-mediated inhibition of IFN-I signaling. This study uncovers the significance of bilirubin metabolism in antiviral innate immunity and demonstrates that conventional IFN-I therapy is less efficient for patients with hepatitis B virus (HBV) with high levels of bilirubin.

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.