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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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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 |
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author | Cardoso, Vânia Chesné, Julie Ribeiro, Hélder García-Cassani, Bethania Carvalho, Tânia Bouchery, Tiffany Shah, Kathleen Barbosa-Morais, Nuno L. Harris, Nicola Veiga-Fernandes, Henrique |
author_facet | Cardoso, Vânia Chesné, Julie Ribeiro, Hélder García-Cassani, Bethania Carvalho, Tânia Bouchery, Tiffany Shah, Kathleen Barbosa-Morais, Nuno L. Harris, Nicola Veiga-Fernandes, Henrique |
author_sort | Cardoso, Vânia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5714273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-57142732018-03-06 Neuronal regulation of type 2 innate lymphoid cells via neuromedin U Cardoso, Vânia Chesné, Julie Ribeiro, Hélder García-Cassani, Bethania Carvalho, Tânia Bouchery, Tiffany Shah, Kathleen Barbosa-Morais, Nuno L. Harris, Nicola Veiga-Fernandes, Henrique Nature Article 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. 2017-09-06 2017-09-14 /pmc/articles/PMC5714273/ /pubmed/28869974 http://dx.doi.org/10.1038/nature23469 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Cardoso, Vânia Chesné, Julie Ribeiro, Hélder García-Cassani, Bethania Carvalho, Tânia Bouchery, Tiffany Shah, Kathleen Barbosa-Morais, Nuno L. Harris, Nicola Veiga-Fernandes, Henrique Neuronal regulation of type 2 innate lymphoid cells via neuromedin U |
title | Neuronal regulation of type 2 innate lymphoid cells via neuromedin U |
title_full | Neuronal regulation of type 2 innate lymphoid cells via neuromedin U |
title_fullStr | Neuronal regulation of type 2 innate lymphoid cells via neuromedin U |
title_full_unstemmed | Neuronal regulation of type 2 innate lymphoid cells via neuromedin U |
title_short | Neuronal regulation of type 2 innate lymphoid cells via neuromedin U |
title_sort | neuronal regulation of type 2 innate lymphoid cells via neuromedin u |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714273/ https://www.ncbi.nlm.nih.gov/pubmed/28869974 http://dx.doi.org/10.1038/nature23469 |
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