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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01-16

AUTHORS

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-Flörl, Fabio Majo, Gabriella Ricciotti, Helmut Ellemunter, Luigi Ratclif, Vincenzo Nicola Talesa, Valerio Napolioni, Luigina Romani

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. More... »

PAGES

14017

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms14017

    DOI

    http://dx.doi.org/10.1038/ncomms14017

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1038129346

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28090087


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