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The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation

Author

Listed:
  • Antonia Wallrapp

    (Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital)

  • Samantha J. Riesenfeld

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Patrick R. Burkett

    (Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital
    Brigham and Women’s Hospital)

  • Raja-Elie E. Abdulnour

    (Brigham and Women’s Hospital)

  • Jackson Nyman

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Danielle Dionne

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Matan Hofree

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Michael S. Cuoco

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Christopher Rodman

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Daneyal Farouq

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Brian J. Haas

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Timothy L. Tickle

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • John J. Trombetta

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Pankaj Baral

    (Harvard Medical School)

  • Christoph S. N. Klose

    (Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, Cornell University)

  • Tanel Mahlakõiv

    (Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, Cornell University)

  • David Artis

    (Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, Cornell University)

  • Orit Rozenblatt-Rosen

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Isaac M. Chiu

    (Harvard Medical School)

  • Bruce D. Levy

    (Brigham and Women’s Hospital)

  • Monika S. Kowalczyk

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard)

  • Aviv Regev

    (Klarman Cell Observatory, Broad Institute of MIT and Harvard
    Howard Hughes Medical Institute and David H. Koch Institute for Integrative Cancer Research, MIT)

  • Vijay K. Kuchroo

    (Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital
    Klarman Cell Observatory, Broad Institute of MIT and Harvard)

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.

Suggested Citation

  • Antonia Wallrapp & Samantha J. Riesenfeld & Patrick R. Burkett & Raja-Elie E. Abdulnour & Jackson Nyman & Danielle Dionne & Matan Hofree & Michael S. Cuoco & Christopher Rodman & Daneyal Farouq & Bria, 2017. "The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation," Nature, Nature, vol. 549(7672), pages 351-356, September.
    • Handle: RePEc:nat:nature:v:549:y:2017:i:7672:d:10.1038_nature24029
    DOI: 10.1038/nature24029
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