Institute of Pathogen Biology and Immunology of College of Biology, Hunan Provincial Key Laboratory of Medical Virology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, Hunan, China.
Institute of Pathogen Biology and Immunology of College of Biology, Hunan Provincial Key Laboratory of Medical Virology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, Hunan, China; Research Center of Cancer Prevention and Treatment, Translational Medicine Research Center of Liver Cancer, Hunan Cancer Hospital, Changsha, Hunan, China.
Cell Rep. 2022 Aug 16;40(7):111215. doi: 10.1016/j.celrep.2022.111215.
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.
干扰素（IFNs）在抗病毒防御、抗肿瘤效应和免疫调节活性中起着至关重要的作用。尽管甲硫氨酸氧化与植物、动物和人类的各种生理和病理生理过程有关，但它在免疫中的作用尚不清楚。我们发现信号转导和转录激活因子 2（STAT2）的氧化还原循环是一个内在的细胞生物学过程，而氧化还原状态的损害导致 STAT2 甲硫氨酸氧化，抑制其激活。IFN 通过募集蛋氨酸亚砜还原酶 MSRB2 来保护 STAT2，蛋氨酸亚砜还原酶 MSRB2 的酶活性在 IFN 处理时被本研究中定义的 STAT2 伴侣 N-乙酰转移酶 9（NAT9）增强。因此，Nat9 的缺失使小鼠更容易感染病毒。我们的研究强调了甲硫氨酸氧化在免疫中的关键作用，为衰老导致免疫功能下降提供了证据，并可能为 IFN 在免疫相关疾病中的临床应用提供思路。
