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 ...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.展开更多
基金supported by grants from the National Natural Science Foundation of China(82001690 to H.C.81925017 and 82130052 to T.L.)the National Key Research and Development Program of China(2020YFA0707703 to T.Z.and 2020YFA0707702 to T.L.).
文摘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.
