The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation
Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs us...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/116796 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826209207899127808 |
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| author | Wallrapp, Antonia Riesenfeld, Samantha J. Burkett, Patrick R. Abdulnour, Raja-Elie E. Nyman, Jackson Dionne, Danielle Hofree, Matan Cuoco, Michael S. Rodman, Christopher Farouq, Daneyal Haas, Brian J. Tickle, Timothy L. Trombetta, John J. Baral, Pankaj Klose, Christoph S. N. Mahlakõiv, Tanel Artis, David Rozenblatt-Rosen, Orit Chiu, Isaac M. Levy, Bruce D. Kowalczyk, Monika S. Regev, Aviv Kuchroo, Vijay K. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Wallrapp, Antonia Riesenfeld, Samantha J. Burkett, Patrick R. Abdulnour, Raja-Elie E. Nyman, Jackson Dionne, Danielle Hofree, Matan Cuoco, Michael S. Rodman, Christopher Farouq, Daneyal Haas, Brian J. Tickle, Timothy L. Trombetta, John J. Baral, Pankaj Klose, Christoph S. N. Mahlakõiv, Tanel Artis, David Rozenblatt-Rosen, Orit Chiu, Isaac M. Levy, Bruce D. Kowalczyk, Monika S. Regev, Aviv Kuchroo, Vijay K. |
| author_sort | Wallrapp, Antonia |
| collection | MIT |
| description | Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33. ILC2s were transcriptionally heterogeneous after activation, with subpopulations distinguished by expression of proliferative, homeostatic and effector genes. The neuropeptide receptor Nmur1 was preferentially expressed by ILC2s at steady state and after IL-25 stimulation. Neuromedin U (NMU), the ligand of NMUR1, activated ILC2s in vitro, and in vivo co-administration of NMU with IL-25 strongly amplified allergic inflammation. Loss of NMU-NMUR1 signalling reduced ILC2 frequency and effector function, and altered transcriptional programs following allergen challenge in vivo. Thus, NMUR1 signalling promotes inflammatory ILC2 responses, highlighting the importance of neuro-immune crosstalk in allergic inflammation at mucosal surfaces. |
| first_indexed | 2024-09-23T14:19:12Z |
| format | Article |
| id | mit-1721.1/116796 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:19:12Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1167962022-09-29T08:41:11Z The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation Wallrapp, Antonia Riesenfeld, Samantha J. Burkett, Patrick R. Abdulnour, Raja-Elie E. Nyman, Jackson Dionne, Danielle Hofree, Matan Cuoco, Michael S. Rodman, Christopher Farouq, Daneyal Haas, Brian J. Tickle, Timothy L. Trombetta, John J. Baral, Pankaj Klose, Christoph S. N. Mahlakõiv, Tanel Artis, David Rozenblatt-Rosen, Orit Chiu, Isaac M. Levy, Bruce D. Kowalczyk, Monika S. Regev, Aviv Kuchroo, Vijay K. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Regev, Aviv Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33. ILC2s were transcriptionally heterogeneous after activation, with subpopulations distinguished by expression of proliferative, homeostatic and effector genes. The neuropeptide receptor Nmur1 was preferentially expressed by ILC2s at steady state and after IL-25 stimulation. Neuromedin U (NMU), the ligand of NMUR1, activated ILC2s in vitro, and in vivo co-administration of NMU with IL-25 strongly amplified allergic inflammation. Loss of NMU-NMUR1 signalling reduced ILC2 frequency and effector function, and altered transcriptional programs following allergen challenge in vivo. Thus, NMUR1 signalling promotes inflammatory ILC2 responses, highlighting the importance of neuro-immune crosstalk in allergic inflammation at mucosal surfaces. 2018-07-05T14:50:24Z 2018-07-05T14:50:24Z 2017-09 2018-07-02T18:44:33Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/116796 Wallrapp, Antonia et al. “The Neuropeptide NMU Amplifies ILC2-Driven Allergic Lung Inflammation.” Nature 549, 7672 (September 2017): 351–356 © 2017 Macmillan Publishers Limited, part of Springer Nature https://orcid.org/0000-0001-8567-2049 http://dx.doi.org/10.1038/NATURE24029 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Wallrapp, Antonia Riesenfeld, Samantha J. Burkett, Patrick R. Abdulnour, Raja-Elie E. Nyman, Jackson Dionne, Danielle Hofree, Matan Cuoco, Michael S. Rodman, Christopher Farouq, Daneyal Haas, Brian J. Tickle, Timothy L. Trombetta, John J. Baral, Pankaj Klose, Christoph S. N. Mahlakõiv, Tanel Artis, David Rozenblatt-Rosen, Orit Chiu, Isaac M. Levy, Bruce D. Kowalczyk, Monika S. Regev, Aviv Kuchroo, Vijay K. The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation |
| title | The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation |
| title_full | The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation |
| title_fullStr | The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation |
| title_full_unstemmed | The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation |
| title_short | The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation |
| title_sort | neuropeptide nmu amplifies ilc2 driven allergic lung inflammation |
| url | http://hdl.handle.net/1721.1/116796 https://orcid.org/0000-0001-8567-2049 |
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