Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response

• Published in: Frontiers in immunology Vol. 12; p. 655637
• Main Authors: Chu, Lei, Li, Chenhui, Li, Yongxing, Yu, Qiuya, Yu, Huansha, Li, Chunhui, Meng, Wei, Zhu, Juanjuan, Wang, Quanyi, Wang, Chen, Cui, Shufang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22.04.2021
• Subjects: autoimmune disease; cyclic GMP-AMP synthase (cGAS); herpes simplex virus type 1 (HSV-1); Immunology; innate immunity; perillaldehyde; herpes simplex virus type 1 (HSV-1); innate immunity; autoimmune disease; cyclic GMP-AMP synthase (cGAS); perillaldehyde
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.655637

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–Goutières 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.