Abstract：
The STING signaling pathway has gained attention over the last few years due to its ability to incite antimicrobial and antitumoral immunity. Conversely, in mouse models of autoimmunity such as colitis and multiple sclerosis, where TH17 cells are implicated in tissue inflammation, STING activation has been associated with the attenuation of immunogenic responses. In this line, STING was found to limit murine TH17 pro-inflammatory program in vitro. Here we demonstrate that 2\'3\'-c-di-AM(PS)2(Rp,Rp), a STING agonist that has been undergoing clinical trials for antitumor immunotherapy, activates the STING signalosome in differentiating human TH17 cells. Of particular interest, 2\'3\'-c-di-AM(PS)2(Rp,Rp) reduces IL-17A production and IL23R expression by human TH17 cells while it favors the generation of regulatory T (Treg) cells. These findings suggest that STING agonists may be promising approaches for treating human TH17-mediated chronic inflammation.
摘要：
STING信号通路在过去几年中由于其激发抗微生物和抗肿瘤免疫的能力而受到关注。相反，在结肠炎和多发性硬化症等自身免疫小鼠模型中，其中TH17细胞与组织炎症有关，STING激活与免疫原性应答的减弱有关。在这行,发现STING在体外限制鼠TH17促炎程序。在这里，我们证明2'3'-c-di-AM(PS)2(Rp，Rp),一种正在进行抗肿瘤免疫疗法临床试验的STING激动剂，在人TH17细胞分化中激活STING信号体。特别感兴趣的是，2\'3\'-c-di-AM(PS)2(Rp，Rp）减少人TH17细胞的IL-17A产生和IL23R表达，同时有利于调节性T（Treg）细胞的产生。这些发现表明STING激动剂可能是治疗人TH17介导的慢性炎症的有希望的方法。
