{Reference Type}: Journal Article
{Title}: Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production.
{Author}: Sun X;Liu L;Wang J;Luo X;Wang M;Wang C;Chen J;Zhou Y;Yin H;Song Y;Xiong Y;Li H;Zhang M;Zhu B;Li X;
{Journal}: Cell Mol Immunol
{Volume}: 21
{Issue}: 7
{Year}: 2024 Jul 28
{Factor}: 22.096
{DOI}: 10.1038/s41423-024-01160-y
{Abstract}: Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells (DCs) and T cells, ultimately leading to increased production of cytokines such as interleukin (IL)-23 and IL-17A. It is established that the cGAS-STING pathway is essential for psoriatic inflammation, however, the specific role of cGAS-STING signaling in DCs within this context remains unclear. In this study, we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod (IMQ)-treated mice. Using a conditional Sting-knockout transgenic mouse model, we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17- and IFN-γ-producing T cells in psoriatic inflammation. Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells, and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model. Furthermore, we explored the therapeutic potential of the STING inhibitor C-176, which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response. Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.