Faculty, Staff and Student Publications
Publication Date
6-20-2024
Journal
Nature Communications
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.
Keywords
Animals, Acid Sensing Ion Channels, Female, Mice, Knockout, Psoriasis, Mice, Calcitonin Gene-Related Peptide, Sensory Receptor Cells, Skin, Imiquimod, Mice, Inbred C57BL, Disease Models, Animal, Inflammation, Neurogenic Inflammation, Humans, Nociceptors, Interleukin-23
DOI
10.1038/s41467-024-49577-3
PMID
38902277
PMCID
PMC11190258
PubMedCentral® Posted Date
6-20-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes