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         description: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.
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      headline:Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production
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      affiliation:
            name:Shanghai University of Traditional Chinese Medicine
            address:
               name:Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
               type:PostalAddress
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            address:
               name:Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
               type:PostalAddress
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      email:[email protected]
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      name:Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
      name:Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
      name:Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
      name:Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
      name:Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
      name:Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
      name:Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
      name:Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
      name:Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
      name:Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
      name:Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
      name:Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
      name:Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, USA
      name:Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
      name:Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China
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      name:Medical Research Institute, Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, China
      name:Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
      name:Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
      name:Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
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