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

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Moretti, Silvia Renga, Giorgia Oikonomou, Vasilis Galosi, Claudia Pariano, Marilena Renauld, Jean-Christophe [UCL] Romani, Luigina

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2017
Language Anglais
Journal information "Nature Communications" - Vol. 8, p. 14017 [1-13] (2017)
Peer reviewed yes
Publisher Nature Publishing Group ((United Kingdom) London)
e-issn 2041-1723
Publication status Publié
Affiliations UCL - SSS/DDUV - Institut de Duve
UCL - SSS/DDUV/MEXP - Médecine expérimentale
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Investigator) Andrew G., Rodriguez-Flores Juan L., Flicek (Principal Investigator) Paul, Clarke Laura, Smith Richard E., Zheng-Bradley Xiangqun, MacArthur (Principal Investigator) Daniel G., Bustamante (Principal Investigator) Carlos D., Gravel Simon, Craig (Principal Investigator) David W., Christoforides Alexis, Homer Nils, Izatt Tyler, Sherry (Principal Investigator) Stephen T., Xiao Chunlin, Dermitzakis (Principal Investigator) Emmanouil T., Abecasis (Principal Investigator) Gonçalo R., Min Kang Hyun, McVean (Principal Investigator) Gil A., Mardis (Principal Investigator) Elaine R., Dooling David, Fulton Lucinda, Fulton Robert, Koboldt Daniel C., Durbin (Principal Investigator) Richard M., Balasubramaniam Senduran, Keane Thomas M., McCarthy Shane, Stalker James, Gerstein (Principal Investigator) Mark B., Balasubramanian Suganthi, Habegger Lukas, Garrison Erik P., Gibbs (Principal Investigator) Richard A., Bainbridge Matthew, Muzny Donna, Yu Fuli, Yu Jin, del Angel Guillermo, Handsaker Robert E., Makarov Vladimir, Rodriguez-Flores Juan L., Jin (Principal Investigator) Hanjun, Kim Wook, Cheol Kim Ki, Flicek (Principal Investigator) Paul, Beal Kathryn, Clarke Laura, Cunningham Fiona, Herrero Javier, McLaren William M., Ritchie Graham R. 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Bibliographic reference Moretti, Silvia ; Renga, Giorgia ; Oikonomou, Vasilis ; Galosi, Claudia ; Pariano, Marilena ; et. al. A mast cell-ILC2-Th9 pathway promotes lung inflammation in cystic fibrosis.. In: Nature Communications, Vol. 8, p. 14017 [1-13] (2017)
Permanent URL http://hdl.handle.net/2078.1/184339