Type I cannabinoid receptor (CB1R) has been reported to exhibit favorable anti-inflammation
and antipruritus effects against inflammation-based skin diseases, but the specific
mechanism remains to be explored. In this study, we found that the activation of CB1R
significantly relieved the scratching behavior and skin inflammation in a psoriatic
mouse model, whereas CB1R antagonist aggravated these symptoms. Because the expression
of CB1R was abundant in dorsal root ganglia, we constructed mice with conditional
CB1R knockout in primary sensory neurons and found that imiquimod-induced psoriasiform
inflammation and itch were both worsened in CB1R-conditional knockout mice. Next,
we observed that the CB1R was mostly located in peptidergic neurons, and deletion
of CB1R in primary sensory neurons promoted the production and release of substance
P to the skin tissue. Furthermore, the elevated substance P in the skin affected the
activation of extracellular signal‒regulated kinase in keratinocytes and induced the
accumulation of mast cells in the dermis. Finally, we showed that blocking the substance
P signal significantly alleviated the exacerbation of psoriasiform inflammation and
itch caused by imiquimod in CB1R-conditional knockout mice. Together, our work reveals
that CB1R in sensory neurons plays a key role in psoriasiform skin inflammation and
pruritus by regulating substance P expression.
Graphical abstract
Graphical Abstract
Abbreviations:
BDNF (brain-derived neurotrophic factor), CB1R (type I cannabinoid receptor), CB1R-cKO (type I cannabinoid receptor‒conditional knockout), CBR (cannabinoid receptor), CGRP (calcitonin gene-related peptide), DRG (dorsal root ganglia), ERK (extracellular signal‒regulated kinase), IMQ (imiquimod), KCs (keratinocytes), MCs (mast cells), SP (substance P), WT (wild type)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: November 18, 2022
Accepted:
October 20,
2022
Received in revised form:
October 18,
2022
Received:
August 24,
2022
accepted manuscript published online XXX; corrected proof published online XXXPublication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
