As the outermost barrier tissue of the body, the skin harbors a large number of innate lymphoid cells (ILCs) that help maintain local homeostasis in the face of changing environments. How skin-resident ILCs are regulated and function in local homeostatic maintenance is poorly understood. We here report the discovery of a cold-sensing neuron-initiated pathway that activates skin group 2 ILCs (ILC2s) to help maintain thermal homeostasis. In stearoyl-CoA desaturase 1 (SCD1) knockout mice whose skin is defective in heat maintenance, chronic cold stress induced excessive activation of CCR10 − CD81 + ST2 + skin ILC2s and associated inflammation. Mechanistically, stimulation of the cold-sensing receptor TRPM8 expressed in sensory neurons of the skin led to increased production of IL-18, which, in turn, activated skin ILC2s to promote thermogenesis. Our findings reveal a neuroimmune link that regulates activation of skin ILC2s to support thermal homeostasis and promotes skin inflammation after hyperactivation.

中文翻译：

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通过冷感 TRPM8 + 神经元衍生信号激活 CD81 + 皮肤 ILC2，维持皮肤热稳态

作为身体最外层的屏障组织，皮肤拥有大量先天淋巴细胞 (ILC)，有助于在面对不断变化的环境时维持局部稳态。人们对皮肤驻留 ILC 的调节及其在局部稳态维持中的功能知之甚少。我们在这里报告了一种冷感知神经元启动通路的发现，该通路可激活皮肤 2 组 ILC (ILC2)，以帮助维持热稳态。在硬脂酰辅酶A去饱和酶1（SCD1）基因敲除小鼠中，其皮肤热量维持有缺陷，慢性冷应激诱导CCR10过度激活-CD81+ST2+皮肤 ILC2 和相关炎症。从机制上讲，刺激皮肤感觉神经元中表达的冷感受体 TRPM8 会导致 IL-18 的产生增加，进而激活皮肤 ILC2 以促进产热。我们的研究结果揭示了调节皮肤 ILC2 激活以支持热稳态并在过度激活后促进皮肤炎症的神经免疫联系。