RT Journal Article
T1 Neuronal regulation of type 2 innate lymphoid cells via neuromedin U
A1 Cardoso, Vânia
A1 Chesné, Julie
A1 Ribeiro, Hélder
A1 García-Cassani, Bethania
A1 Carvalho, Tânia
A1 Bouchery, Tiffany
A1 Shah, Kathleen
A1 Barbosa-Morais, Nuno L.
A1 Harris, Nicola
A1 Veiga-Fernandes, Henrique
AB 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.
PB Springer Nature Group
YR 2017
FD 2017-09-14
LK https://hdl.handle.net/20.500.14352/115960
UL https://hdl.handle.net/20.500.14352/115960
LA eng
NO Cardoso V, Chesné J, Ribeiro H, García-Cassani B, Carvalho T, Bouchery T, Shah K, Barbosa-Morais NL, Harris N, Veiga-Fernandes H. Neuronal regulation of type 2 innate lymphoid cells via neuromedin U. Nature. 2017 Sep 14;549(7671):277-281. doi: 10.1038/nature23469. Epub 2017 Sep 6. PMID: 28869974; PMCID: PMC5714273.
NO Fundacao para a Ciencia e a Tecnologia (FCT)
NO Fondation pour la Recherche Medicale
NO European Union (EU)
NO FP7, EU
NO European Molecular Biology Organization (EMBO)
NO Swiss National Science Foundation (SNSF)
NO ERC, EU
NO Kenneth Rainin Foundation, USA
NO Crohn's and Colitis Foundation of America, USA
DS Docta Complutense
RD 16 abr 2025