IRF3 Promotes Asthma Pathogenesis by Regulating Type 2 Innate Lymphoid Cells

Allergic asthma is characterized by airway hyperresponsiveness triggered by inhaled allergens. Type 2 innate lymphoid cells (ILC2s) have been demonstrated to play a crucial role in promoting airway inflammation through the secretion of type 2 effector cytokines. However, the mechanisms underlying the functions of lung ILC2s remain unclear. In this study, we investigated the expression of IRF3 in ILC2s in both human patients and mouse models of asthma. We utilized IRF3-deficient mice to assess the impact of IRF3 deficiency on ILC2 function in a model of IL33-induced asthma. Additionally, we explored the mechanisms underlying IRF3-mediated regulation of ILC2s, focusing on the involvement of the transcription factor Gata3. Our findings revealed elevated expression of IRF3 in ILC2s of patients and mice with asthma, suggesting a potential role for IRF3 in the pathogenesis of allergic asthma. Furthermore, we demonstrated that IRF3 deficiency impairedthe expansion and function of ILC2s in IL33-induced asthma, highlighting the importance of IRF3 in regulating ILC2-mediated responses. Importantly, we showed that the regulation of ILC2s by IRF3 was independent of Th2 cells and mediated by the transcription factor Gata3. This study identifies IRF3 as a novel regulator of lung ILC2s and suggests its potential as a promising immunotherapeutic target for allergic asthma. These findings shed light on the intricate mechanisms underlying asthma pathogenesis and provide insights into potential strategies for the development of targeted therapies for this prevalent airway disease.