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<p>Group 2 innate lymphoid cells (ILC2) initiate pathologic type 2 inflammation in allergic asthma in response to diverse tissue-derived stimuli. However, the molecular mechanisms by which ILC2 cells integrate and respond to environmental signals are unclear. Here, we show in a mouse model that in allergic asthma, mechanistic target of rapamycin complex 1 (mTORC1) activation in lung ILC2&#xa0;cells increases. Genetic ablation of Raptor, an obligatory component of mTORC1 complex, results in reduced IL-5 and IL-13 production in ILC2 cells and protects mice from allergic inflammation. Pharmacological inhibition of mTORC1 by rapamycin suppresses ILC2 activation and ameliorates allergic lung inflammation. Mechanistically, mTORC1 activation upregulates neuromedin U receptor 1 (NMUR1) expression through epigenetic reprogramming, which augments ILC2 activation in response to neuromedin U (NMU). However, our experiments suggest that NMUR1 is not an exclusive mediator of ILC2 activation downstream of mTORC1. In conclusion, our work reveals that in ILC2s, mTORC1 signaling coordinates neuro-immune crosstalk for optimal activation, and highlights mTORC1 as a potential therapeutic target for allergic asthma.</p>

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mTORC1 signaling in group 2 innate lymphoid cells coordinates neuro-immune crosstalk in allergic lung inflammation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月29日

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  • Dongdi Wang,
  • Lin Hu,
  • Jinyu Chen,
  • Jinxin Qiu,
  • Yue Chen,
  • Michelle Zhang,
  • Linfeng Zhao,
  • Xiaohui Su,
  • Jiping Sun,
  • Ju Qiu,
  • Wei Tang,
  • Wenyong Zhou,
  • Lei Shen

摘要

Group 2 innate lymphoid cells (ILC2) initiate pathologic type 2 inflammation in allergic asthma in response to diverse tissue-derived stimuli. However, the molecular mechanisms by which ILC2 cells integrate and respond to environmental signals are unclear. Here, we show in a mouse model that in allergic asthma, mechanistic target of rapamycin complex 1 (mTORC1) activation in lung ILC2 cells increases. Genetic ablation of Raptor, an obligatory component of mTORC1 complex, results in reduced IL-5 and IL-13 production in ILC2 cells and protects mice from allergic inflammation. Pharmacological inhibition of mTORC1 by rapamycin suppresses ILC2 activation and ameliorates allergic lung inflammation. Mechanistically, mTORC1 activation upregulates neuromedin U receptor 1 (NMUR1) expression through epigenetic reprogramming, which augments ILC2 activation in response to neuromedin U (NMU). However, our experiments suggest that NMUR1 is not an exclusive mediator of ILC2 activation downstream of mTORC1. In conclusion, our work reveals that in ILC2s, mTORC1 signaling coordinates neuro-immune crosstalk for optimal activation, and highlights mTORC1 as a potential therapeutic target for allergic asthma.