Transmembrane protein TMEM184B is necessary for interleukin-31-induced itch.
Transmembrane protein TMEM184B is necessary for interleukin-31-induced itch.
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DOI：
10.1097/j.pain.0000000000002452
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发表时间：
2022-05-01
期刊：
影响因子：
7.4
通讯作者：
Bhattacharya MRC
中科院分区：
文献类型：
--
作者：
Larsen EG;Cho TS;McBride ML;Feng J;Manivannan B;Madura C;Klein NE;Wright EB;Wickstead ES;Garcia-Verdugo HD;Jarvis C;Khanna R;Hu H;Largent-Milnes TM;Bhattacharya MRC
背部根神经节（DRG）中的伤害性神经元分别向脊髓传递疼痛和瘙痒的感觉，分别是一个成熟的DRG神经元的亚型，完成了6-8％的神经元的神经元，包括急性iTch和Athop intery-prerctic cytopcine的传感器。在此不清楚ONS。轴突退化和神经终末维持需要大量的瘙痒接收器，包括IL-31，白细胞三烯C4和组胺缺乏TMEM184B的小鼠。降低IL-31诱导钙进入可能是对这种表型的贡献。 ES成人的体质通过发育Wnt信号传导并促进适当的质感基因表达。
Nociceptive and pruriceptive neurons in the dorsal root ganglia (DRG) convey sensations of pain and itch to the spinal cord, respectively. One subtype of mature DRG neurons, comprising 6–8% of neurons in the ganglia, is responsible for sensing mediators of acute itch and atopic dermatitis, including the cytokine IL-31. How itch-sensitive (pruriceptive) neurons are specified is unclear. Here we show that TMEM184B, a gene with roles in axon degeneration and nerve terminal maintenance, is required for the expression of a large cohort of itch receptors, including those for IL-31, Leukotriene C4, and Histamine. Male and female mice lacking TMEM184B show reduced responses to IL-31, but maintain normal responses to pain and mechanical force, indicating a specific behavioral defect in IL-31 induced pruriception. Calcium imaging experiments indicate that a reduction in IL-31 induced calcium entry is a likely contributor to this phenotype. We identify an early failure of proper Wnt-dependent transcriptional signatures and signaling components in Tmem184b mutant mice that may explain the improper DRG neuronal subtype specification. Accordingly, lentiviral re-expression of TMEM184B in mutant embryonic neurons restores Wnt signatures. Together, these data demonstrate that TMEM184B promotes adult somatosensation through developmental Wnt signaling and promotion of proper pruriceptive gene expression. Our data illuminate a new key regulatory step in the processes controlling the establishment of diversity in the somatosensory system.
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