MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel

作者：Lu, Ping; Zhao, Yonghui; Xie, Zili; Zhou, Huan; Dong, Xinzhong; Wu, Gregory F.; Kim, Brian S.; Feng, Jing^*; Hu, Hongzhen^*

来源：Cell Reports, 2023, 42(4): 112283.

DOI：10.1016/j.celrep.2023.112283

• BEHAVIORAL-RESPONSES
• MOUSE MODEL
• ITCHY SKIN
• TRPA1
• SUBPOPULATION
• MECHANOTRANSDUCTION
• NOCICEPTORS
• NEURONS
• PATHWAY
• TOUCH

Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1-and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced allokne-sis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, through activation of the phospholipase C (PLC) and protein kinase C-8 (PKC8) signaling. Collectively, our data find a TRPV1+/ MrgprA3+ prurioceptor-Piezo2 signaling axis in the initiation of pruritogen-induced mechanical itch sensiti-zation in the skin.

• 单位
  中国科学院研究生院; 南方医科大学