Regulation of group 2 innate lymphoid cells

Viral respiratory tract infections are the major causative agent of infection-induced asthma onset and asthma exacerbations. Despite their medical and economic impact, the mechanisms that regulate these conditions and associated pathologies remain elusive. Here we show that deficiency of type I interferon (IFN) receptor signaling in a mouse model of influenza infection results in infection-associated type 2 immunopathology and tissue fibrosis driven by deregulated priming of group 2 innate lymphoid cells (ILC2). Type I IFNs directly regulated ILC2 in an IFN-stimulated gene factor 3 (ISGF3)-dependent manner that led to reduced expression of GATA binding protein 3 (GATA3), altered cytokine production and cell proliferation, as well as increased cell death. Type I IFNs further induced IFNg in vivo, which directly altered ILC2 function in a signal transducer and activator of transcription 1 (STAT1)-dependent manner. Collectively, these results demonstrate that type I and type II IFNs synergistically restrict ILC2 and thereby limit type 2 immunopathology and fibrotic disease.