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

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, Teresa Zelante, Jean Christophe Renauld, Oxana Bereshchenko, Paolo Sportoletti, Vincenzina Lucidi, Maria Chiara Russo, Carla Colombo, Ersilia Fiscarelli, Cornelia Lass-FlörlFabio Majo, Gabriella Ricciotti, Helmut Ellemunter, Luigi Ratclif, Vincenzo Nicola Talesa, Valerio Napolioni, Luigina Romani

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number14017
JournalNature Communications
Volume8
DOIs
Publication statusPublished - Jan 16 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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