IL-13 deficiency exacerbates lung damage and impairs epithelial-derived type 2 molecules during nematode infection

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-alpha 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.

Automated summary

IL-13 plays a critical role in limiting tissue injury and hemorrhaging in the lung during acute lung damage. Through proteomic and transcriptomic profiling analysis, IL-13-dependent changes in matrix remodeling and epithelial cell responses were identified. IL-13 is also required for the induction of epithelial-derived type 2 effector molecules and cellular stress responses in the context of acute lung damage.