1. Sensory ASIC3 channel exacerbates psoriatic inflammation via a neurogenic pathway in female mice.
- Author
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Huang C, Sun PY, Jiang Y, Liu Y, Liu Z, Han SL, Wang BS, Huang YX, Ren AR, Lu JF, Jiang Q, Li Y, Zhu MX, Yao Z, Tian Y, Qi X, Li WG, and Xu TL
- Subjects
- Animals, Female, Mice, Skin metabolism, Skin pathology, Imiquimod, Mice, Inbred C57BL, Disease Models, Animal, Inflammation metabolism, Neurogenic Inflammation metabolism, Humans, Nociceptors metabolism, Interleukin-23 metabolism, Interleukin-23 genetics, Acid Sensing Ion Channels metabolism, Acid Sensing Ion Channels genetics, Mice, Knockout, Psoriasis metabolism, Psoriasis pathology, Psoriasis genetics, Psoriasis chemically induced, Calcitonin Gene-Related Peptide metabolism, Calcitonin Gene-Related Peptide genetics, Sensory Receptor Cells metabolism
- Abstract
Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management., (© 2024. The Author(s).)
- Published
- 2024
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