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mTORC1 controls ILC2 activation and allergic lung inflammation through NMUR1-mediated neuronal regulation

GSE272521 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/10/30 Platform GPL21273
Summary
Group 2 innate lymphoid cells (ILC2s) play critical roles in allergic lung inflammation through initiating and amplifying type 2 immune responses. However, the molecular mechanisms underlying pathogenic ILC2 activation remain largely unknown. Here, we show that lung ILC2s exhibit increased mTORC1 activation in allergic asthma. Genetic ablation of RAPTOR, an adaptor protein of the mTORC1 complex, results in reduced IL-5 and IL-13 production in ILC2s and protects mice from allergic inflammation. Pharmacological inhibition of mTORC1 by rapamycin also suppresses ILC2 pathogenic activation and ameliorates allergic lung inflammation. Mechanistically, mTORC1 signaling promotes ILC2 activation through metabolic regulation of epigenetics to maintain neurointerin U receptor 1 (NMUR1) expression, which mediates neural-ILC2 interaction via the NMU-NMUR1 axis. These findings identify mTORC1 as a novel regulator to control the neural-ILC2 interaction and highlight mTORC1 as a potential therapeutic target for allergic asthma.
Published in
mTORC1 signaling in group 2 innate lymphoid cells coordinates neuro-immune crosstalk in allergic lung inflammation
Wang D, Hu L, Chen J et al. · Nature communications 2025 · PMID 41318705 · doi:10.1038/s41467-025-66683-y
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Also filed as BioProject PRJNA1137283 and SRA study SRP520721. Searching any of these in the dataset finder brings you back here.

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