Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells

Simon Rauber, Markus Luber, Stefanie Weber, Lisa Maul, Alina Soare, Thomas Wohlfahrt, Neng Yu Lin, Katharina DIetel, Aline Bozec, Martin Herrmann, Mark H. Kaplan, Benno Weigmann, Mario M. Zaiss, Ursula Fearon, Douglas J. Veale, Juan D. Cañete, Oliver DIstler, Felice Rivellese, Costantino Pitzalis, Markus F. NeurathAndrew N.J. McKenzie, Stefan Wirtz, Georg Schett, Jörg H.W. DIstler, Andreas Ramming

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77 Scopus citations

Abstract

Inflammatory diseases such as arthritis are chronic conditions that fail to resolve spontaneously. While the cytokine and cellular pathways triggering arthritis are well defined, those responsible for the resolution of inflammation are incompletely characterized. Here we identified interleukin (IL)-9-producing type 2 innate lymphoid cells (ILC2s) as the mediators of a molecular and cellular pathway that orchestrates the resolution of chronic inflammation. In mice, the absence of IL-9 impaired ILC2 proliferation and activation of regulatory T (T reg) cells, and resulted in chronic arthritis with excessive cartilage destruction and bone loss. In contrast, treatment with IL-9 promoted ILC2-dependent T reg activation and effectively induced resolution of inflammation and protection of bone. Patients with rheumatoid arthritis in remission exhibited high numbers of IL-9 + ILC2s in joints and the circulation. Hence, fostering IL-9-mediated ILC2 activation may offer a novel therapeutic approach inducing resolution of inflammation rather than suppression of inflammatory responses.

Original languageEnglish (US)
Pages (from-to)938-944
Number of pages7
JournalNature Medicine
Volume23
Issue number8
DOIs
StatePublished - Aug 1 2017

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Rauber, S., Luber, M., Weber, S., Maul, L., Soare, A., Wohlfahrt, T., Lin, N. Y., DIetel, K., Bozec, A., Herrmann, M., Kaplan, M. H., Weigmann, B., Zaiss, M. M., Fearon, U., Veale, D. J., Cañete, J. D., DIstler, O., Rivellese, F., Pitzalis, C., ... Ramming, A. (2017). Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells. Nature Medicine, 23(8), 938-944. https://doi.org/10.1038/nm.4373