1. Cutaneous Calcium/Calmodulin-Dependent Protein Kinase II-γ-Positive Sympathetic Nerves Secreting Norepinephrine Dictate Psoriasis.
- Author
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Yu Y, Chen W, Li B, Li Z, Wang Y, Mao Y, Fan W, Bai Y, Hu H, Zhen Q, and Sun L
- Subjects
- Animals, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Calcium-Calmodulin-Dependent Protein Kinase Type 2 genetics, Imiquimod, Interleukin-17 metabolism, Mice, Inbred C57BL, Skin metabolism, Skin innervation, Disease Models, Animal, Norepinephrine metabolism, Psoriasis metabolism, Sympathetic Nervous System metabolism
- Abstract
Cutaneous sympathetic nerve is a crucial part of neuropsychiatric factors contributing to skin immune response, but its role in the psoriasis pathogenesis remains unclear. It is found that cutaneous calcium/calmodulin-dependent protein kinase II-γ (CAMK2γ), expressed mainly in sympathetic nerves, is activated by stress and imiquimod in mouse skin. Camk2g-deficient mice exhibits attenuated imiquimod-induced psoriasis-like manifestations and skin inflammation. CaMK2γ regulates dermal γδT-cell interleukin-17 production in imiquimod-treated mice, dependent on norepinephrine production following cutaneous sympathetic nerve activation. Adrenoceptor β1, the primary skin norepinephrine receptor, colocalises with γδT cells. CaMK2γ aggravates psoriasiform inflammation via sympathetic nerve-norepinephrine-γδT cell-adrenoceptor β1-nuclear factor-κB and -p38 axis activation. Application of alcaftadine, a small-molecule CaMK2γ inhibitor, relieves imiquimod-induced psoriasis-like manifestations in mice. This study reveals the mechanisms of sympathetic-nervous-system regulation of γδT-cell interleukin-17 secretion, and provides insight into neuropsychiatric factors dictating psoriasis pathogenesis and new potential targets for clinical psoriasis treatment., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)
- Published
- 2024
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