Suppression of neuropeptide by botulinum toxin improves imiquimod-induced psoriasis-like dermatitis via the regulation of neuroimmune system.

[BACKGROUND] Psoriasis is a multifactorial disease arises from a complex interaction of genetics, immune system, and environmental aspects. IL-23/Th17 immune axis has been considered as a primary modulator in psoriasis. In addition, several findings imply that nervous system may take a part in the pathogenesis of psoriasis, suggesting that nervous system, through its neuropeptide, may interact with immune system and lead to the formation of psoriasis.

[OBJECTIVE] We aimed to ascertain the role of neuropeptides secreted from neurons in the pathogenesis of psoriasis in vivo.

[METHODS] The release of neuropeptide was inhibited by injecting Botulinum toxin B (BTX-B) on Imiquimod (IMQ)-induced psoriasis-like dermatitis mice model. Quantification of skin dermatitis, infiltrating inflammatory cells, and the production of cytokines at the lesional skin area were performed by PSI score, immunostaining, and real-time PCR. We also tested the effect of selective CGRP antagonist (CGRP) on psoriasis-like dermatitis in IMQ-treated mice.

[RESULTS] BTX-B injection significantly suppressed PSI score and reduced the number of CD4 T cells, CD11c dendritic cells, and the production of IL-17A/F in the lesional skin. The expressions of PGP9.5 nerve fibers and neuropeptides (SP, CGRP) were also significantly reduced following BTX-B injection. Additionally, CGRP antagonist also suppressed the development of IMQ-induced psoriasis-like dermatitis in mice.

[CONCLUSION] The suppression of neuropeptide secretion in the skin by BTX injection might inhibit nerve elongation, the infiltration of immune cells, as well as IL-17 production, resulting in the improvement of psoriasis. Neuropeptide inhibitor could also be applied to the treatment of psoriasis.