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

Alistair Chenery, Silvia Rosini, James E Parkinson, Jesuthas Ajendra, Jeremy Herrera, Craig Lawless, Brian H K Chan, P'ng Loke, Andrew S MacDonald, Karl E Kadler, Tara E Sutherland, Judith E Allen

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10 Citations (Scopus)
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Abstract

IL-13 is implicated in effective repair following acute lung injury as well as 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.
Original languageEnglish
Article numbere202001000
Number of pages14
JournalLife Science Alliance
Volume4
Issue number8
DOIs
Publication statusPublished - 14 Jun 2021

Bibliographical note

Acknowledgements
This work was supported by the Wellcome Trust (203128/Z/16/Z, 110126/Z/
15/Z, and 106898/A/15/Z) and the Medical Research Council UK (MR/
K01207X/2). TE Sutherland was supported by Medical Research Founda-
tion UK joint funding with Asthma UK (MRFAUK-2015-302). We thank Andrew
McKenzie (Cambridge) for providing the Il13 tm3.1Anjm mice. We further thank
the Flow Cytometry, Bioimaging, Genomic Technologies, BioMS, and Bio-
logical Services core facilities at the University of Manchester.

Data Availability Statement

Data Availability
The mass spectrometry proteomics data have been deposited to
the ProteomeXchange Consortium via the PRIDE (Perez-Riverol
et al, 2019) partner repository with the dataset identifier PXD021853

Supplementary Information is available at https://doi.org/10.26508/lsa.
202001000.

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