复旦大学Tao Li等研究人员合作发现，吲哚美辛通过抑制IRF3的核转位抑制胞质核酸刺激的免疫反应。相关论文于2024年4月5日在线发表在《分子细胞生物学杂志》上。

研究人员报告了一种广泛使用的非甾体抗炎药物吲哚美辛能抑制核酸触发的I型干扰素（IFN）产生。研究人员发现，吲哚美辛能有效阻断DNA和RNA刺激的IFN表达。有趣的是，吲哚美辛还能抑制IRF3在细胞核酸识别后的核转位。重要的是，在细胞系和Aicardi–Goutières综合征小鼠模型中，吲哚美辛能减弱自身DNA诱导的自身免疫反应。

因此，该研究揭示了吲哚美辛以前未知的功能，并为胞质核酸刺激的自身免疫提供了一种潜在的治疗方法。

据悉，胞质核酸的识别会触发DNA/RNA传感器-IRF3轴介导的IFN产生，IFN是抗病毒免疫反应所需的。然而，这些信号通路的不适当激活与自身免疫疾病有关。

附：英文原文

Title: Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3

Author: Wang, Miao, Li, Xiao-Wei, Yuan, Sen-Chao, Pan, Jie, Guo, Zeng-Lin, Sun, Li-Ming, Jiang, Shao-Zhen, Zhao, Ming, Xue, Wen, Cai, Hong, Gu, Lin, Luo, Dan, Chen, Ling, Zhou, Xue-Qing, Han, Qiu-Ying, Li, Jin, Zhou, Tao, Xia, Tian, Li, Tao

Issue&Volume: 2024-04-05

Abstract: The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor–IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi–Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

DOI: 10.1093/jmcb/mjae015

Source: https://dx.doi.org/10.1093/jmcb/mjae015