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A mast cell-ILC2-Th9 pathway promotes lung inflammation in cystic fibrosis

Author

Listed:
  • Silvia Moretti

    (University of Perugia)

  • Giorgia Renga

    (University of Perugia)

  • Vasilis Oikonomou

    (University of Perugia)

  • Claudia Galosi

    (University of Perugia)

  • Marilena Pariano

    (University of Perugia)

  • Rossana G. Iannitti

    (University of Perugia)

  • Monica Borghi

    (University of Perugia)

  • Matteo Puccetti

    (University of Perugia)

  • Marco De Zuani

    (University of Udine)

  • Carlo E. Pucillo

    (University of Udine)

  • Giuseppe Paolicelli

    (University of Perugia)

  • Teresa Zelante

    (University of Perugia)

  • Jean-Christophe Renauld

    (Ludwig Institute for Cancer Research, Brussels Branch)

  • Oxana Bereshchenko

    (Section of Pharmacology, University of Perugia)

  • Paolo Sportoletti

    (Institute of Haematology-CREO (Centro di Ricerche Emato-Oncologiche), Ospedale S. Maria Misericordia)

  • Vincenzina Lucidi

    (Unit of Endocrinology and Diabetes, Bambino Gesù Children's Hospital)

  • Maria Chiara Russo

    (Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan)

  • Carla Colombo

    (Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan)

  • Ersilia Fiscarelli

    (Bambino Gesù Children's Hospital IRCCS)

  • Cornelia Lass-Flörl

    (Innsbruck Medical University)

  • Fabio Majo

    (Unit of Endocrinology and Diabetes, Bambino Gesù Children's Hospital)

  • Gabriella Ricciotti

    (Bambino Gesù Children's Hospital IRCCS)

  • Helmut Ellemunter

    (CF Centre, Medical University Innsbruck)

  • Luigi Ratclif

    (Servizio di Supporto Fibrosi Cistica, Istituto Ospedale G. Tatarella)

  • Vincenzo Nicola Talesa

    (University of Perugia)

  • Valerio Napolioni

    (University of Perugia)

  • Luigina Romani

    (University of Perugia)

Abstract

T helper 9 (Th9) cells contribute to lung inflammation and allergy as sources of interleukin-9 (IL-9). However, the mechanisms by which IL-9/Th9 mediate immunopathology in the lung are unknown. Here we report an IL-9-driven positive feedback loop that reinforces allergic inflammation. We show that IL-9 increases IL-2 production by mast cells, which leads to expansion of CD25+ type 2 innate lymphoid cells (ILC2) and subsequent activation of Th9 cells. Blocking IL-9 or inhibiting CD117 (c-Kit) signalling counteracts the pathogenic effect of the described IL-9-mast cell-IL-2 signalling axis. Overproduction of IL-9 is observed in expectorates from cystic fibrosis (CF) patients, and a sex-specific variant of IL-9 is predictive of allergic reactions in female patients. Our results suggest that blocking IL-9 may be a therapeutic strategy to ameliorate inflammation associated with microbial colonization in the lung, and offers a plausible explanation for gender differences in clinical outcomes of patients with CF.

Suggested Citation

  • Silvia Moretti & Giorgia Renga & Vasilis Oikonomou & Claudia Galosi & Marilena Pariano & Rossana G. Iannitti & Monica Borghi & Matteo Puccetti & Marco De Zuani & Carlo E. Pucillo & Giuseppe Paolicelli, 2017. "A mast cell-ILC2-Th9 pathway promotes lung inflammation in cystic fibrosis," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14017
    DOI: 10.1038/ncomms14017
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