Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33. ILC2s were transcriptionally heterogeneous after activation, with subpopulations distinguished by expression of proliferative, homeostatic and effector genes. The neuropeptide receptor Nmur1 was preferentially expressed by ILC2s at steady state and after IL-25 stimulation. Neuromedin U (NMU), the ligand of NMUR1, activated ILC2s in vitro, and in vivo co-administration of NMU with IL-25 strongly amplified allergic inflammation. Loss of NMU–NMUR1 signalling reduced ILC2 frequency and effector function, and altered transcriptional programs following allergen challenge in vivo. Thus, NMUR1 signalling promotes inflammatory ILC2 responses, highlighting the importance of neuro-immune crosstalk in allergic inflammation at mucosal surfaces.

中文翻译：

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神经肽 NMU 放大 ILC2 驱动的过敏性肺部炎症

2 型先天淋巴细胞 (ILC2) 有助于粘膜稳态并引发过敏性哮喘的病理性炎症。然而，指导 ILC2 促进体内平衡与炎症的信号尚不清楚。为了识别这些分子线索，我们使用单细胞 RNA 测序在稳态和用警报细胞因子 IL-25 和 IL-33 进行体内刺激后对小鼠肺驻留 ILC 进行了分析。ILC2s 在激活后在转录上是异质的，亚群通过增殖、稳态和效应基因的表达来区分。神经肽受体 Nmur1 在稳态和 IL-25 刺激后优先由 ILC2s 表达。Neuromedin U (NMU) 是 NMUR1 的配体，在体外激活 ILC2s，在体内联合使用 NMU 与 IL-25 会强烈放大过敏性炎症。NMU-NMUR1 信号的缺失降低了 ILC2 频率和效应子功能，并改变了体内过敏原挑战后的转录程序。因此，NMUR1 信号促进炎症性 ILC2 反应，突出了神经免疫串扰在粘膜表面过敏性炎症中的重要性。