IL-33 delivery induces serous cavity macrophage proliferation independent of interleukin-4 receptor alpha

Lucy H Jackson-Jones, Dominik Rückerl, Freya Svedberg, Sheelagh Duncan, Rick M Maizels, Tara E Sutherland, Stephen J Jenkins, Henry J McSorley, Cécile Bénézech, Andrew S MacDonald, Judith E Allen

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30 Citations (Scopus)


IL-33 plays an important role in the initiation of type-2 immune responses, as well as the enhancement of type 2 effector functions. Engagement of the IL-33 receptor on macrophages facilitates polarization to an alternative activation state by amplifying IL-4 and IL-13 signaling to IL-4Rα. IL-4 and IL-13 also induce macrophage proliferation but IL-33 involvement in this process has not been rigorously evaluated. As expected, in vivo delivery of IL-33 induced IL-4Rα-dependent alternative macrophage activation in the serous cavities. IL-33 delivery also induced macrophages to proliferate but, unexpectedly, this was independent of IL-4Rα signalling. In a filarial nematode infection model in which IL-4Rα-dependent alternative activation and proliferation in the pleural cavity is well described, IL-33R was essential for alternative activation but not macrophage proliferation. Similarly, during Alternaria alternata induced airway inflammation, which provokes strong IL-33 responses, we observed that both IL-4Rα and IL-33R were required for alternative activation, while macrophage proliferation in the pleural cavity was still evident in the absence of either receptor alone. Our data show that IL-33R and IL-4Rα promote macrophage proliferation independently of each other, but both are essential for induction of alternative activation. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)2311–2321
JournalEuropean Journal of Immunology
Issue number10
Publication statusPublished - 1 Oct 2016

Bibliographical note

This article is protected by copyright. All rights reserved.

Acknowledgements: We would like to thank Dr Martin Waterfall and Dr Gareth Howell for assistance with flow cytometry and Imagestream, respectively, Clare Lloyd, Frank Brombacher, and Andrew McKenzie for kind provision of mouse lines and the University of Edinburgh and University of Manchester veterinarians and support staff for excellent animal husbandry. ImageStream analysis was carried out using the MRC Single Cell Genomics Facility at the University of Manchester. L.H.J.-J. designed and performed experiments, analyzed data and wrote the manuscript. D.R. provided critical ideas and techniques. F.S. performed experiments and analyzed data. S.D. performed experiments. T.E.S. & S.J.J. provided critical ideas. R.M.M. provided essential new tools. H.J.M. provided critical ideas and essential new tools. C.B. performed experiments and provided critical ideas. A.S.M. facilitated the research. J.E.A. facilitated the research, designed experiments and wrote the manuscript. This work was supported by Medical Research Council UK grants to J.E.A. (MR/K01207X/1) and C.B. (MR/M011542/1).


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