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-17...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.展开更多
基金supported by China National Natural Science Foundation(grant nos.82374445,82303061,82305233 and 82373179)Shanghai Shuguang Scholar(grant no.22SG42)+3 种基金Scientific research project of Shanghai Municipal Health Commission(grant no.20224Z0019)Key Discipline Construction Project of Shanghai Three Year Action Plan for Strengthening the Construction of Public Health System(grant no.GWVI-11.1-24)High-level Chinese Medicine Key Discipline Construction Project(Integrative Chinese and Western Medicine Clinic)of National Administration of TCM(grant no.zyyzdxk-2023065)Evidence-based dermatology base sponsored by state Administration of Traditional Chinese medicine.
文摘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.
