Cargando…

Neuronal regulation of type 2 innate lymphoid cells via neuromedin U

Group 2 innate lymphoid cells (ILC2s) regulate inflammation, tissue repair and metabolic homeostasis1. ILC2 activation is driven by host-derived cytokines and alarmins1. While discrete immune cell subsets integrate nervous system cues2–4, it remains unclear whether neuronal-derived signals control I...

Descripción completa

Detalles Bibliográficos
Autores principales: Cardoso, Vânia, Chesné, Julie, Ribeiro, Hélder, García-Cassani, Bethania, Carvalho, Tânia, Bouchery, Tiffany, Shah, Kathleen, Barbosa-Morais, Nuno L., Harris, Nicola, Veiga-Fernandes, Henrique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714273/
https://www.ncbi.nlm.nih.gov/pubmed/28869974
http://dx.doi.org/10.1038/nature23469
Descripción
Sumario:Group 2 innate lymphoid cells (ILC2s) regulate inflammation, tissue repair and metabolic homeostasis1. ILC2 activation is driven by host-derived cytokines and alarmins1. While discrete immune cell subsets integrate nervous system cues2–4, it remains unclear whether neuronal-derived signals control ILC2s. Here we show that Neuromedin U (NMU) is a uniquely fast and potent regulator of type 2 innate immunity in the context of a novel neuron-ILC2 unit. We found that ILC2s selectively express Neuromedin U receptor 1 (Nmur1), while mucosal neurons express NMU. ILC2-autonomous activation with NMU resulted in immediate and strong production of innate inflammatory and tissue repair cytokines, in a NMUR1-dependent manner. NMU controlled ILC2s downstream of extracellular signal–regulated kinase (ERK) and calcium (Ca(2+))-influx-dependent activation of 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 worm infection control. Strikingly, mucosal neurons were found adjacent to ILC2s, directly sensed worm products and alarmins to induce NMU and to control innate type 2 cytokines. Our work reveals that neuron-ILC2 cell units are poised to confer a first-line of immediate tissue protection via coordinated neuro-immune sensory responses.