Qiu-Ying Han

Abstract Systemic lupus erythematosus (SLE) has a complex, multifactorial etiology, which contributes to a lack of definitive cure and limited treatment efficacy. Here, we report that cyclic GMP-AMP synthase (cGAS) is significantly activated in SLE patients. We further demonstrate that cGAS deletion protects mice from lupus-like symptoms induced by the TLR7 agonist imiquimod (IMQ). In a screen of 3,159 FDA-approved drugs, we identify the antiplatelet agent prasugrel as a potent cGAS inhibitor.

Wild-type and Trex1−/− Sprague Dawley (SD) rats were obtained from Nanjing Biomedical Research Institute of Nanjing University based on CRISPR-Cas9 technology. The guide RNA sequence is as follows: 5′-GTCCACCACACGGGGTGGTT-3′. All rats were housed on a 12 h light/dark cycle with ad libitum access to food and water.

Hong Cai, Xin Liu, Feng Zhang, Qiu-Ying Han, Zhao-Shan Liu, Wen Xue, Zeng-Lin Guo, Jiang-Man Zhao, Li-Ming Sun, Na Wang, Jie Mao, Kun He, Tian Xia, Yuan Chen, Liang Chen, Ai-Ling Li, Tao Zhou, Xue-Min Zhang, Wei-Hua Li and Tao Li J Immunol May 15, 2021, 206 (10) 2453-2467; DOI: https://doi.org/10.4049/jimmunol.2001111 Key Points G3BP1 deletion dampens the intracellular nucleic acid sensing. G3BP1 inhibition alleviates nucleic acid–induced immune responses.