无感受性感官神经元驱动interleukin-23-介导的牛皮形皮肤炎症
Lorena Riol-Blanco1, Jose Ordovas-Montanes1, Mario Perro2
11] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA [2].
Nature
|April 25, 2014
概括
感觉神经元,特别是TRPV1(+) Nav1.8(+) 感觉受体,通过与皮肤树突细胞 (DDC) 相互作用来控制皮肤炎症. 这种相互作用调节IL-23的产生,影响IL-17通路和在类似牛皮的病症中免疫细胞的招募.
科学领域:
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
- 皮肤病学 皮肤病学
背景情况:
- 皮肤充当屏障和感官器官,容纳皮肤树突细胞 (DDC) 和γδ T (γδT17) 细胞等免疫细胞.
- 这些细胞因IL-23的异常激活会导致类似牛皮的炎症.
- 周围神经在调节皮肤免疫反应中的作用尚不清楚.
研究的目的:
- 研究外周神经,特别是感官神经元在调节皮肤炎症中的作用.
- 阐明感觉神经元影响IL-23产生和随后皮肤炎症反应的机制.
主要方法:
- 小鼠的皮肤被暴露在伊米基莫德中,以诱导依赖IL-23的牛皮状炎症.
- 选择性药理或基因废除感知受体 (TRPV1(+) Nav1.8(+) 感觉神经元) 进行.
- 完整皮肤的成像被用来评估DDCs和 nociceptors之间的接触.
- 用IL-23进行皮内注射,以评估其独立于 nociceptors 的效果.
主要成果:
- 发现表达TRPV1和Nav1.8的感觉神经元的一个子集对于驱动因米基基莫德诱导的皮肤炎症至关重要.
- 皮肤树突细胞 (DDC) 经常被观察到与这些恶感受体密切接触.
- 消去 nociceptors 显著减少了 DDCs 的 IL-23 生产和随后的 IL-17 驱动的炎症.
- 皮内IL-23注射恢复了炎症,绕过了 nociceptor-DDC通信的需要.
结论:
- TRPV1 ((+) Nav1.8 ((+) nociceptors 在启动和调节皮肤炎症方面发挥着至关重要的作用.
- 鼻受体与DDC相互作用,控制IL-23的产生,从而调节IL-23/IL-17通路.
- 这些发现揭示了皮肤中的新型神经免疫轴,该轴调节皮肤免疫反应.
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