Journal Article

Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response

Cui, Shufang, Li, Chenhui, Chu, Lei, Li, Yongxing, Li, Chunhui, Wang, Quanyi, Wang, Chen, Yu, Qiuya, Meng, Wei, Yu, Huansha, Zhu, Juanjuan

2021

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Antibodies / autoimmune disease / Autoimmune diseases / Autoimmunity / cyclic GMP-AMP synthase (cGAS) / Cytokines / Deoxyribonucleic acid / DNA / Herpes simplex / herpes simplex virus type 1 (HSV-1) / Herpes viruses / Immune response / Immunology / Inflammatory diseases / Innate immunity / Interferon / Kinases / Laboratory animals / Lupus / Manufacturers / Medical research / Pathogens / Penicillin / perillaldehyde / Protease inhibitors / Viral infections