IRF-7 Is a Critical Regulator of Type 2 Innate Lymphoid Cells in Allergic Airway Inflammation

Abstract

Allergic asthma is a highly prevalent airway disease triggered by hyperresponsiveness to inhaled allergens. Interferon regulatory factor 7 (IRF7) has been shown to be highly expressed in nasal aspirates from children with asthma. Type 2 innate lymphoid cells (ILC2s) represent the major player in allergic airway inflammation. The role of IRF7 in ILC2-driven asthma remains to be explored. Here, we report that IRF7 expression in murine lung ILC2s is dramatically induced upon papain or interleukin-33 (IL-33) stimulation. ILC2s from asthma patients display a much higher level of IRF7 than those from healthy donors. Deficiency of IRF7 in mice significantly impairs the expansion and function of lung ILC2s in multiple models of allergic asthma. Furthermore, the regulation of ILC2s by IRF7 is cell intrinsic and mediated by the transcription factor Bcl11b. These observations identify IRF7 as a regulator of lung ILC2s, which may have immunotherapeutic value in allergic asthma.

Keywords: Alternaria alternate; Bcl11b; IL-33; allergic airway inflammation; asthma; interferon regulatory factor 7; papain; type 2 innate lymphoid cells.