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  3. The key role of CB1R in the sensory neurons to regulate psoriasiform skin inflammation and pruritus

The key role of CB1R in the sensory neurons to regulate psoriasiform skin inflammation and pruritus

  • J Invest Dermatol. 2022 Nov 18;S0022-202X(22)02770-1. doi: 10.1016/j.jid.2022.10.014.
Xin Liu 1,  Li Li 2,  Jian Jiang 1,  Wenqiang Ge 3,  Yuqiong Huang 1,  Zilin Jin 1,  XinXin Liu 1,  Yi Kong 1,  Ouyang Zhanmu 3,  Xin Zeng 4,  Fei Li 4,  Man Li 3,  Hongxiang Chen 5
Affiliations

Affiliations

  • 1 Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, JieFang Avenue No.1277, Wuhan, Hubei Province, 430030, China.
  • 2 Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, XiWu Road No.157, Xi'an, Shanxi Province, 710004, China.
  • 3 Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, HangKong Road No.13, Wuhan, Hubei Province, 430030, China.
  • 4 Department of Dermatology, Union Shenzhen Hospital, Huazhong University of Science and Technology, TaoYuan Road No.89, Shenzhen, Guangdong Province, 518052, China.
  • 5 Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, JieFang Avenue No.1277, Wuhan, Hubei Province, 430030, China; Department of Dermatology, Union Shenzhen Hospital, Huazhong University of Science and Technology, TaoYuan Road No.89, Shenzhen, Guangdong Province, 518052, China. Electronic address: [email protected].
PMID: 36410425 DOI: 10.1016/j.jid.2022.10.014
Abstract

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.

Keywords

inflammation; pruritus; psoriasis; sensory neuron; substance P; type I cannabinoid receptor.

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