Open AccessType I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells
Author(s) -
Claudia U. Duerr,
Connor D A McCarthy,
Barbara C. Mindt,
Manuel Rubio,
Alexandre P. Meli,
Julien Pothlichet,
Megan M. Eva,
JeanFrançois Gauchat,
Salman T. Qureshi,
Bruce Mazer,
Karen L. Mossman,
Danielle Malo,
Ana M. Gamero,
Silvia M. Vidal,
Irah L. King,
Marika Sarfati,
Jörg H. Fritz
Publication year - 2015
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/ni.3308
Subject(s) - innate lymphoid cell , immunology , biology , interferon , cytokine , immunopathology , stat1 , innate immune system , irf1 , interferon gamma , transcription factor , immune system , gene , genetics
Viral respiratory tract infections are the main causative agents of the onset of infection-induced asthma and asthma exacerbations that remain mechanistically unexplained. Here we found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology. Type I interferons directly and negatively regulated mouse and human ILC2 cells in a manner dependent on the transcriptional activator ISGF3 that led to altered cytokine production, cell proliferation and increased cell death. In addition, interferon-γ (IFN-γ) and interleukin 27 (IL-27) altered ILC2 function dependent on the transcription factor STAT1. These results demonstrate that type I and type II interferons, together with IL-27, regulate ILC2 cells to restrict type 2 immunopathology.