期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.655637
关键词
cyclic GMP-AMP synthase (cGAS); perillaldehyde; herpes simplex virus type 1 (HSV-1); innate immunity; autoimmune disease
类别
资金
- National Natural Science Foundation of China [31801076, 81802000]
- Natural Science Foundation of the Jiangsu province [BK20180555]
- China Postdoctoral Science Foundation [2018M630641]
- National Key R&D Program of China [2016YFA0501800]
- Project Program of State Key Laboratory of Natural Medicines [SKLNMZZ202002]
- Double First-Class Project of China Pharmaceutical University [CPU2018GF10]
The study found that perillaldehyde (PAH) derived from Perilla frutescens can suppress cytosolic-DNA-induced innate immune responses by inhibiting cGAS activity, potentially benefiting the treatment of autoimmune diseases.
Cyclic GMP-AMP synthase (cGAS), serving as a primary sensor of intracellular DNA, is essential to initiate anti-microbial innate immunity. Inappropriate activation of cGAS by self-DNA promotes severe autoinflammatory diseases such as Aicardi-Goutieres syndrome (AGS); thus, inhibition of cGAS may provide therapeutic benefit in anti-autoimmunity. Here we report that perillaldehyde (PAH), a natural monoterpenoid compound derived from Perilla frutescens, suppresses cytosolic-DNA-induced innate immune responses by inhibiting cGAS activity. Mice treated with PAH are more susceptible to herpes simplex virus type 1 (HSV-1) infection. Moreover, administration with PAH markedly ameliorates self-DNA-induced autoinflammatory responses in a mouse model of AGS. Collectively, our study reveals that PAH can effectively inhibit cGAS-STING signaling and could be developed toward the treatment of cGAS-mediated autoimmune diseases.
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