Abstract
IL-13 is implicated in effective repair after acute lung injury and the pathogenesis of chronic diseases such as allergic asthma. Both these processes involve matrix remodelling, but understanding the specific contribution of IL-13 has been challenging because IL-13 shares receptors and signalling pathways with IL-4. Here, we used Nippostrongylus brasiliensis infection as a model of acute lung damage comparing responses between WT and IL-13-deficient mice, in which IL-4 signalling is intact. We found that IL-13 played a critical role in limiting tissue injury and haemorrhaging in the lung, and through proteomic and transcriptomic profiling, identified IL-13-dependent changes in matrix and associated regulators. We further showed a requirement for IL-13 in the induction of epithelial-derived type 2 effector molecules such as RELM-α and surfactant protein D. Pathway analyses predicted that IL-13 induced cellular stress responses and regulated lung epithelial cell differentiation by suppression of Foxa2 pathways. Thus, in the context of acute lung damage, IL-13 has tissue-protective functions and regulates epithelial cell responses during type 2 immunity.
Highlights
IL-13 is a central effector cytokine with diverse roles during both protective and pathogenic type 2 immune responses
After infection with N. brasiliensis, WT mice had increased Il13 mRNA expression in the lung on day 2 post-infection (D2pi) that further increased by D6pi (Fig 1A)
Upon gross inspection of lung sections from D2pi, it was evident that infected Il13−/− lungs had larger gaps in the alveoli, presumably in IL-13 deficiency and acute lung injury Chenery et al
Summary
IL-13 is a central effector cytokine with diverse roles during both protective and pathogenic type 2 immune responses. IL-13 is critical for goblet cell hyperplasia and mucus production at mucosal sites (Finkelman et al, 2004). These responses are essential for the expulsion of gastrointestinal worms from the host (Shimokawa et al, 2017). IL-4 signals through the type I receptor (IL-4Rα paired with the common γ chain) and the type II receptor (IL-4Rα paired with IL-13Rα1) whereas IL-13 only signals through the type II receptor. Understanding the individual roles of these two cytokines has important clinical implications
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