2. Academic Validation
  3. Postprandial parasympathetic signals promote lung type 2 immunity

Postprandial parasympathetic signals promote lung type 2 immunity

  • Neuron. 2025 Mar 5;113(5):670-683.e7. doi: 10.1016/j.neuron.2024.12.020.
Hongjie Chen 1,  Xin Zhou 2,  Tingting Liu 1,  Jiaqi Liu 1,  Di Wu 3,  Xia Xu 4,  Shanwu Ma 5,  Guangliang Qiang 5,  Jian Chen 3,  Ying Cao 6,  Wei Fu 7,  Jing Yang 8
Affiliations

Affiliations

  • 1 PTN Graduate Program, Peking University Third Hospital Cancer Center, Center for Life Sciences, IDG/McGovern Institute for Brain Research, State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China.
  • 2 PTN Graduate Program, Peking University Third Hospital Cancer Center, Center for Life Sciences, IDG/McGovern Institute for Brain Research, State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; Department of General Surgery, Peking University Third Hospital, Beijing 100191, China.
  • 3 Chinese Institute for Brain Research, Beijing 102206, China.
  • 4 Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
  • 5 Department of Thoracic Surgery, Peking University Third Hospital, Beijing 100191, China.
  • 6 PTN Graduate Program, Peking University Third Hospital Cancer Center, Center for Life Sciences, IDG/McGovern Institute for Brain Research, State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China. Electronic address: caoying@pku.edu.cn.
  • 7 PTN Graduate Program, Peking University Third Hospital Cancer Center, Center for Life Sciences, IDG/McGovern Institute for Brain Research, State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; Department of General Surgery, Peking University Third Hospital, Beijing 100191, China. Electronic address: fuwei@bjmu.edu.cn.
  • 8 PTN Graduate Program, Peking University Third Hospital Cancer Center, Center for Life Sciences, IDG/McGovern Institute for Brain Research, State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; Peking Union Medical College Hospital, Beijing 100730, China. Electronic address: jing.yang@pku.edu.cn.
PMID: 39837323 DOI: 10.1016/j.neuron.2024.12.020
Abstract

Lung type 2 immunity protects against pathogenic Infection, but its dysregulation causes asthma. Although it has long been observed that symptoms of asthmatic patients often become exaggerated following food intake, the pathophysiological mechanism underlying this postprandial phenomenon is incompletely understood. Here, we report that lung type 2 immunity in mice is enhanced after feeding, which correlates with parasympathetic activation. Also, local parasympathetic innervations exhibit spatial engagement with such immune responses mediated by group 2 innate lymphoid cells (ILC2s). Pharmacologic or surgical blockage of parasympathetic signals diminishes lung type 2 immunity. Conversely, chemogenetic manipulation of parasympathetic inputs and their upstream neurocircuit is sufficient to modulate those immune responses. We then show that the cholinergic receptor muscarinic 4 (Chrm4) for the parasympathetic neurotransmitter acetylcholine is expressed in mouse or human lung ILC2s, and the Chrm4 deletion mitigates ILC2-mediated lung inflammation. These results have revealed a critical neuroimmune function of the gut-brain-lung reflex.

Keywords

Chrm4; ILC2s; cholinergic receptor muscarinic 4; food intake; group 2 innate lymphoid cells; lung type 2 immunity; parasympathetic signal.

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