078 TRPV4 regulates the IL-23/Th17 pathways in imiquimod-induced psoriasis-like lesion through the production of ATP and neuropeptide

Psoriasis is a chronic inflammatory skin disease with complex mechanism that involves the activity of different type cells. Along IL-23/Th17 axis, nervous system plays an important role in development psoriasis. Transient receptor potential vanilloid 4 (TRPV4) ion channel Ca2+-permeable nonselective cation channels express keratinocytes, nerve fibers, and immune cells skin. Recently, we found increased expression TRPV4 human psoriasis site. We hypothesized activation would play significant The objective was to investigate involvement pathogenesis Imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model utilized wild knockout (KO) mice. severity significantly lower KO mice compared WT from day 3 6 (p<0.01). Histopathological studies showed epidermal thickness number infiltrated CD3+ T CD68+ macrophages were reduced mice, along IL-17A, IL-17F IL-23 (p<0.05 for each). Moreover, level ATP neuropeptides, such as Substance P, Calcitonin gene-related peptide, neuron marker PGP9.5 decreased (p <0.05). proliferative capacity production heat or air-stimulated TRPV4-deficient keratinocytes inhibited vitro. Finally, administration antagonist (HC-067047) prevented IMQ-treated In conclusion, might involve axis through neuropeptides increase proliferation keratinocyte. have be new therapeutic target