%0 Journal Article
%T Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production.
%A Sun X
%A Liu L
%A Wang J
%A Luo X
%A Wang M
%A Wang C
%A Chen J
%A Zhou Y
%A Yin H
%A Song Y
%A Xiong Y
%A Li H
%A Zhang M
%A Zhu B
%A Li X
%J Cell Mol Immunol
%V 21
%N 7
%D 2024 Jul 28
%M 38806624
%F 22.096
%R 10.1038/s41423-024-01160-y
%X 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.