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 (Lead / Corresponding author)

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19 Citations (Scopus)
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Abstract

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 signaling. 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.

Original languageEnglish
Pages (from-to)2311-2321
Number of pages11
JournalEuropean Journal of Immunology
Volume46
Issue number10
Early online date5 Sep 2016
DOIs
Publication statusPublished - Oct 2016

Keywords

  • Alternaria
  • IL-33
  • IL-4
  • Macrophage
  • Nematode
  • Proliferation

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