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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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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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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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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DOI: https://doi.org/10.1038/ni.2133
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