Abstract
Here we describe a reporter mouse strain designed to map the fate of cells that have activated interleukin 17A (IL-17A). We found that IL-17-producing helper T cells (TH17 cells) had distinct plasticity in different inflammatory settings. Chronic inflammatory conditions in experimental autoimmune encephalomyelitis (EAE) caused a switch to alternative cytokines in TH17 cells, whereas acute cutaneous infection with Candida albicans did not result in the deviation of TH17 cells to the production of alternative cytokines, although IL-17A production was shut off in the course of the infection. During the development of EAE, interferon-γ (IFN-γ) and other proinflammatory cytokines in the spinal cord were produced almost exclusively by cells that had produced IL-17 before their conversion by IL-23 ('ex-TH17 cells'). Thus, this model allows the actual functional fate of effector T cells to be related to TH17 developmental origin regardless of IL-17 expression.
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Acknowledgements
We thank J.-C. Renauld (Ludwig Institute for Cancer Research) for monoclonal antibody AM22.3; the Large Scale Facility of the Medical Research Council National Institute for Medical Research for growing C. albicans; G. Preece for cell sorting; and Biological Services (Medical Research Council National Institute for Medical Research) for breeding and maintenance of our mouse strains. Supported by the Medical Research Council UK (U117512792 to B.S. and U117563359 to A.J.P.) and the European Research Council (ref. 232782).
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K.H., J.H.D., H.A. and C.W. designed and did experiments; M.V., E.H., Y.L., M.T., U.M. and A.G. were involved in generating the construct, targeting embryonic stem cells and injections; D.J.C. provided IL-23p19-deficient mice; and A.J.P. and B.S. designed experiments and wrote the paper.
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Hirota, K., Duarte, J., Veldhoen, M. et al. Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol 12, 255–263 (2011). https://doi.org/10.1038/ni.1993
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DOI: https://doi.org/10.1038/ni.1993
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