IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis

Rossana G. Iannitti, Valerio Napolioni, Vasilis Oikonomou, Antonella De Luca, Claudia Galosi, Marilena Pariano, Cristina Massi-Benedetti, Monica Borghi, Matteo Puccetti, Vincenzina Lucidi, Carla Colombo, Ersilia Fiscarelli, Cornelia Lass-Flörl, Fabio Majo, Lisa Cariani, Maria Russo, Luigi Porcaro, Gabriella Ricciotti, Helmut Ellemunter, Luigi RatclifFernando Maria De Benedictis, Vincenzo Nicola Talesa, Charles A. Dinarello, Frank L. Van De Veerdonk, Luigina Romani

Research output: Contribution to journalArticle

Abstract

Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurrs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF.

Original languageEnglish
Article number10791
JournalNature Communications
Volume7
DOIs
Publication statusPublished - Mar 14 2016

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ASJC Scopus subject areas

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

Cite this

Iannitti, R. G., Napolioni, V., Oikonomou, V., De Luca, A., Galosi, C., Pariano, M., Massi-Benedetti, C., Borghi, M., Puccetti, M., Lucidi, V., Colombo, C., Fiscarelli, E., Lass-Flörl, C., Majo, F., Cariani, L., Russo, M., Porcaro, L., Ricciotti, G., Ellemunter, H., ... Romani, L. (2016). IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis. Nature Communications, 7, [10791]. https://doi.org/10.1038/ncomms10791