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An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation

Nature Immunology volume 12, pages 1071–1077 (2011)Cite this article

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Abstract

Interleukin 9 (IL-9) is a cytokine linked to lung inflammation, but its cellular origin and function remain unclear. Here we describe a reporter mouse strain designed to map the fate of cells that have activated IL-9. We found that during papain-induced lung inflammation, IL-9 production was largely restricted to innate lymphoid cells (ILCs). IL-9 production by ILCs depended on IL-2 from adaptive immune cells and was rapidly lost in favor of other cytokines, such as IL-13 and IL-5. Blockade of IL-9 production via neutralizing antibodies resulted in much lower expression of IL-13 and IL-5, which suggested that ILCs provide the missing link between the well-established functions of IL-9 in the regulation of type 2 helper T cell cytokines and responses.

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Figure 1: Papain-induced eYFP+ cells do not express lineage markers.
Figure 2: IL-9 expression by ILCs is transient.
Figure 3: IL-9 in ILCs is induced by IL-2 but not by IL-25, IL-33 or TSLP.
Figure 4: Intranasal challenge with IL-33 induces ILCs poised for IL-9 production.
Figure 5: IL-9 expression in ILCs depends on IL-2 and the adaptive immune system.
Figure 6: ILCs are the main source of IL-9.
Figure 7: IL-9 promotes cytokine expression in ILCs.

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Acknowledgements

We thank M. Wilson and A. Potocnik for advice and discussion and the Division of Biological Services for breeding and maintenance of our mouse strains. Supported by the Medical Research Council UK (U117512792) and Sonderforschungsbereich (SFB 587 to T.S. and K.L.).

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Authors and Affiliations

  1. Division of Molecular Immunology, Medical Research Council (MRC) National Institute for Medical Research, Mill Hill, UK

    Christoph Wilhelm, Keiji Hirota, Mauro Tolaini & Brigitta Stockinger

  2. Division of Molecular Structure, MRC National Institute for Medical Research, Mill Hill, UK

    Benjamin Stieglitz

  3. Ludwig Institute for Cancer Research, Brussels, Belgium

    Jacques Van Snick

  4. Department of Pathology, Laboratory of Immunology and Vascular Biology, Stanford University School of Medicine, Stanford, California, USA

    Katharina Lahl

  5. Twincore, Institut für Infektionsimmunologie, Hannover, Germany

    Katharina Lahl & Tim Sparwasser

  6. London School of Hygiene and Tropical Medicine, London, UK

    Helena Helmby

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Contributions

C.W. designed and did the experiments and wrote the manuscript; K.H. provided advice and contributed to experiments; B.S. purified neutralizing antibodies; K.L. and T.S. provided help and advice for the BAC construct; J.V.S. provided reagents; M.T. did the BAC injections; H.H. provided advice; and B.S. designed experiments and wrote the manuscript.

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Correspondence to Brigitta Stockinger.

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Wilhelm, C., Hirota, K., Stieglitz, B. et al. An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation. Nat Immunol 12, 1071–1077 (2011). https://doi.org/10.1038/ni.2133

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