RRC ID 49638
Author Wallrapp A, Riesenfeld SJ, Burkett PR, Abdulnour RE, Nyman J, Dionne D, Hofree M, Cuoco MS, Rodman C, Farouq D, Haas BJ, Tickle TL, Trombetta JJ, Baral P, Klose CSN, Mahlakõiv T, Artis D, Rozenblatt-Rosen O, Chiu IM, Levy BD, Kowalczyk MS, Regev A, Kuchroo VK.
Title The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation.
Journal Nature
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.
Volume 549(7672)
Pages 351-356
Published 2017-9-21
DOI 10.1038/nature24029
PII nature24029
PMID 28902842
PMC PMC5746044
MeSH Animals Female Gene Expression Regulation Hypersensitivity / immunology* Hypersensitivity / pathology* Immunity, Innate / immunology Inflammation / immunology* Inflammation / pathology* Interleukin-17 / immunology Interleukin-33 / immunology Ligands Lung / immunology Lung / pathology* Lymphocytes / immunology* Male Mice Mice, Inbred C57BL Neuropeptides / metabolism* Receptors, Neurotransmitter / biosynthesis Receptors, Neurotransmitter / genetics Receptors, Neurotransmitter / metabolism Respiratory Mucosa / immunology Respiratory Mucosa / pathology Signal Transduction Transcription, Genetic
IF 42.779
Times Cited 182
Mice RBRC04549