The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation
Name
nihms927364.pdf
Size
2.02 MB
Format
Adobe PDF
Checksum (MD5)
2f4bbee49a3e85aaeddbc383a1670c1b
Author(s)
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
Date Issued
September 2017
Journal
Nature
Publisher
Nature Publishing Group
Citation
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
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
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.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/NATURE24029
