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Neuronal regulation of type 2 innate lymphoid cells via neuromedin U
Open accessAbstract
Group 2 innate lymphoid cells (ILC2s) regulate inflammation, tissue repair and metabolic homeostasis, and are activated by host-derived cytokines and alarmins. Discrete subsets of immune cells integrate nervous system cues, but it remains unclear whether neuron-derived signals control ILC2s. Here we show that neuromedin U (NMU) in mice is a fast and potent regulator of type 2 innate immunity in the context of a functional neuron-ILC2 unit. We found that ILC2s selectively express neuromedin U receptor 1 (Nmur1), and mucosal neurons express NMU. Cell-autonomous activation of ILC2s with NMU resulted in immediate and strong NMUR1-dependent production of innate inflammatory and tissue repair cytokines. NMU controls ILC2s downstream of extracellular signal-regulated kinase and calcium-influx-dependent activation of both calcineurin and nuclear factor of activated T cells (NFAT). NMU treatment in vivo resulted in immediate protective type 2 responses. Accordingly, ILC2-autonomous ablation of Nmur1 led to impaired type 2 responses and poor control of worm infection. Notably, mucosal neurons were found adjacent to ILC2s, and these neurons directly sensed worm products and alarmins to induce NMU and to control innate type 2 cytokines. Our work reveals that neuron-ILC2 cell units confer immediate tissue protection through coordinated neuroimmune sensory responses.
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“For example, activation of type 2 innate lymphoid cells (ILC2) in the gut mucosa is regulated by neuronally-derived peptides, with neuromedin U initiating102, and α-calcitonin gene-related peptide (αCGRP) antagonizing, type 2 immunity103.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [102]
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Metadata
- Authors
- Cardoso, V., Chesné, J., Ribeiro, H., García-Cassani, B., Carvalho, T., Bouchery, T., Shah, K., Barbosa-Morais, N. L., Harris, N., & Veiga-Fernandes, H.
- Affiliations
- University of Lisbon (PT)
- École Polytechnique Fédérale de Lausanne (CH)
- ORCID
- Venue
- Nature
- Published
- 2017-09-06
- Volume
- 549
- Issue
- 7671
- Pages
- 277-281
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5714273
- OpenAlex
- W2750992365
- Cited by
- 592
- References
- 44
- Citations by year
- 2026: 53 · 2025: 69 · 2024: 50 · 2023: 46 · 2022: 79 · 2021: 70 · 2020: 70 · 2019: 79 · 2018: 67 · 2017: 9
- FWCI
- 27.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Funders
- Crohn's and Colitis Foundation (313089)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (156517, 310030)
- Medical Research Council (MR/R024812/1)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Keywords
- ILC2, neuromedin U, enteric neurons, neuroimmune interactions, Nippostrongylus brasiliensis, Th2 immune response, tissue repair, calcineurin, NFAT, ERK signaling, alarmins, gastrointestinal nematode infection, mucosal immunity
- MeSH terms
- Animals, Calcium, Female, Immunity, Innate, Lymphocytes, Male, Mice, Inbred C57BL, Neurons, Neuropeptides, Nippostrongylus, Cytokines, Strongylida Infections, Receptors, Neurotransmitter, Calcineurin, MAP Kinase Signaling System, NFATC Transcription Factors, Mice
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