Tanshinone IIA alleviates myocarditis in Trex1-D18N lupus-like mice by inhibiting the interaction between STING and SEC24C.

Abstract

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway serves as a crucial component of the innate immune defense, playing a vital role in combating pathogen invasion. However, its dysregulation or abnormal activation can trigger the development of autoimmune diseases. This study demonstrated that Tanshinone IIA, a major lipid-soluble component of Salvia miltiorrhiza Bunge, can effectively inhibit the activation of the cGAS-STING signaling pathway. Mechanistically, Tanshinone IIA inhibits the transport of STING from the ER to the Golgi apparatus by weakening the interaction between STING and SEC24C, thereby preventing the activation of the cGAS-STING signaling pathway. Furthermore, Tanshinone IIA significantly ameliorated myocardial inflammation in WT and Trex1mice. Our research indicates that Tanshinone IIA shows potential therapeutic value in alleviating autoimmune diseases by effectively inhibiting the abnormal activation of the cGAS-STING pathway.