The redox cycling of STAT2 maintains innate immune homeostasis

作者：Binbin Xue, Huiyi Li, Shun Liu, Qing Feng, Yan Xu, Rilin Deng, Shengwen Chen, Jingjing Wang, Xinran Li, Mengyu Wan, Songqing Tang, Haizhen Zhu · 发表于：Cell Reports · 年份：2022 · DOI：10.1016/j.celrep.2022.111215 · 被引用次数：12 · 研究领域：Immune Cell Function and Interaction、Redox biology and oxidative stress、Genomics, phytochemicals, and oxidative stress

Interferons (IFNs) are essential in antiviral defense, antitumor effects, and immunoregulatory activities. Although methionine oxidation is associated with various physiological and pathophysiological processes in plants, animals, and humans, its role in immunity remains unclear. We find that the redox cycling of signal transducer and activator of transcription 2 (STAT2) is an intrinsic cellular biological process, and that impairment of the redox status contributes to STAT2 methionine oxidation, inhibiting its activation. IFN protects STAT2 from methionine oxidation through the recruitment of methionine sulfoxide reductase MSRB2, whose enzymatic activity is enhanced by N-acetyltransferase 9 (NAT9), a chaperone of STAT2 defined in this study, upon IFN treatment. Consequently, loss of Nat9 renders mice more susceptible to viral infection. Our study highlights the key function of methionine oxidation in immunity, which provides evidence for the decline of immune function by aging and may provide insights into the clinical applications of IFN in immune-related diseases.