Chen Changchun, Itakura Eisuke, Nelson Geoffrey M, Sheng Ming, Laurent Patrick, Fenk Lorenz A, Butcher Rebecca A, Hegde Ramanujan S, de Bono Mario
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Department of Chemistry, University of Florida, Gainesville, Florida 32611, USA.
Nature. 2017 Feb 2;542(7639):43-48. doi: 10.1038/nature20818. Epub 2017 Jan 18.
Interleukin-17 (IL-17) is a major pro-inflammatory cytokine: it mediates responses to pathogens or tissue damage, and drives autoimmune diseases. Little is known about its role in the nervous system. Here we show that IL-17 has neuromodulator-like properties in Caenorhabditis elegans. IL-17 can act directly on neurons to alter their response properties and contribution to behaviour. Using unbiased genetic screens, we delineate an IL-17 signalling pathway and show that it acts in the RMG hub interneurons. Disrupting IL-17 signalling reduces RMG responsiveness to input from oxygen sensors, and renders sustained escape from 21% oxygen transient and contingent on additional stimuli. Over-activating IL-17 receptors abnormally heightens responses to 21% oxygen in RMG neurons and whole animals. IL-17 deficiency can be bypassed by optogenetic stimulation of RMG. Inducing IL-17 expression in adults can rescue mutant defects within 6 h. These findings reveal a non-immunological role of IL-17 modulating circuit function and behaviour.
白细胞介素-17（IL-17）是一种主要的促炎细胞因子：它介导对病原体或组织损伤的反应，并引发自身免疫性疾病。人们对其在神经系统中的作用知之甚少。在此，我们表明IL-17在秀丽隐杆线虫中具有类似神经调节剂的特性。IL-17可直接作用于神经元，改变其反应特性及对行为的贡献。通过无偏向性遗传筛选，我们描绘了一条IL-17信号通路，并表明它在RMG中枢中间神经元中发挥作用。破坏IL-17信号会降低RMG对来自氧气传感器输入的反应性，并使从21%氧气环境中的持续逃避变得短暂且依赖于额外刺激。过度激活IL-17受体会异常增强RMG神经元和整个动物对21%氧气的反应。通过对RMG进行光遗传学刺激可绕过IL-17缺陷。在成虫中诱导IL-17表达可在6小时内挽救突变体缺陷。这些发现揭示了IL-17调节神经回路功能和行为的非免疫作用。
