Papers of the Week

Type I cannabinoid receptor (CB1R) has been reported to exhibit favorable anti-inflammation and anti-pruritus 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 psoriatic mouse model, while CB1R antagonist aggravated these symptoms. As the expression of CB1R was abundant in dorsal root ganglia (DRG), we constructed mice with conditional CB1R knockout (CB1R-cKO) in primary sensory neurons and found that imiquimod (IMQ) induced psoriasiform inflammation and itch were both worsened in CB1R-cKO mice. Next, we observed that the CB1R mostly located in peptidergic neurons and deletion of CB1R in primary sensory neurons promoted the production and release of substance P (SP) to the skin tissue. Furthermore, the elevated SP in the skin affected the activation of ERK in keratinocytes and induced the accumulation of mast cells in the dermis. Last, we demonstrated that blocking the SP signal significantly alleviated the exacerbation of psoriasiform inflammation and itch caused by IMQ in CB1R-cKO mice. Together, our work reveals that CB1R in sensory neurons plays a key role in psoriasiform skin inflammation and pruritus via regulating SP expression.