Signaling through stimulator of interferon genes (STING) leads to the production of type I interferons (IFN-Is) and inflammatory cytokines. A gain-of-function mutation in STING was identified in an autoinflammatory disease (STING-associated vasculopathy with onset in infancy; SAVI). The expression of cyclic GMP-AMP, DNA-activated cGAS-STING pathway, increased in a proportion of patients with SLE. The STING signaling pathway may be a candidate for targeted therapy in SLE. Here, we demonstrated that disruption of STING signaling ameliorated lupus development in Fcgr2b-deficient mice. Activation of STING promoted maturation of conventional dendritic cells and differentiation of plasmacytoid dendritic cells via LYN interaction and phosphorylation. The inhibition of LYN decreased the differentiation of STING-activated dendritic cells. Adoptive transfer of STING-activated bone marrow-derived dendritic cells into the FCGR2B and STING double-deficiency mice restored lupus phenotypes. These findings provide evidence that the inhibition of STING signaling may be a candidate targeted treatment for a subset of patients with SLE.

通过干扰素基因刺激物（STING）发出的信号导致产生I型干扰素（IFN-Is）和炎性细胞因子。在自体炎症性疾病（婴儿期发作的STING相关血管病； SAVI）中发现了STING的功能获得性突变。SLE患者中环状GMP-AMP（DNA激活的cGAS-STING途径）的表达增加。STING信号传导途径可以是SLE中靶向治疗的候选者。在这里，我们证明了STING信号的破坏改善了Fcgr2b中狼疮的发生缺陷的小鼠。STING的激活通过LYN相互作用和磷酸化促进了常规树突状细胞的成熟和浆细胞样树突状细胞的分化。LYN的抑制降低了STING激活的树突状细胞的分化。STING激活的骨髓来源树突状细胞过继转移到FCGR2B和STING双缺​​陷小鼠中恢复了狼疮的表型。这些发现提供了证据，即STING信号传导的抑制可能是针对部分SLE患者的候选靶向治疗。