Abstract
Interleukin 17 (IL-17)-producing helper T cells (TH17 cells) require exposure to IL-23 to become encephalitogenic, but the mechanism by which IL-23 promotes their pathogenicity is not known. Here we found that IL-23 induced production of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in TH17 cells and that GM-CSF had an essential role in their encephalitogenicity. Our findings identify a chief mechanism that underlies the important role of IL-23 in autoimmune diseases. IL-23 induced a positive feedback loop whereby GM-CSF secreted by TH17 cells stimulated the production of IL-23 by antigen-presenting cells. Such cross-regulation of IL-23 and GM-CSF explains the similar pattern of resistance to autoimmunity when either of the two cytokines is absent and identifies TH17 cells as a crucial source of GM-CSF in autoimmune inflammation.
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Acknowledgements
We thank KaloBios Pharmaceuticals for anti-GM-CSF; P. Gonnella for critical review; K. Regan for editorial assistance; and S. Yu for technical assistance. Supported by the US National Institutes of Health, the National Multiple Sclerosis Society and the M.E. Groff Foundation.
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M.E.-B. designed and did most of the experiments and wrote the manuscript; B.C. designed and did experiments, wrote the manuscript and supervised the study; H.D., Y.Y., M.C. and F.S. did experiments; G.-X.Z. wrote the manuscript; B.N.D. provided MBP(Ac1–11) TCR-transgenic and Csf2−/− mice; and A.R. designed experiments, wrote the manuscript and supervised the study.
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El-Behi, M., Ciric, B., Dai, H. et al. The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 12, 568–575 (2011). https://doi.org/10.1038/ni.2031
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DOI: https://doi.org/10.1038/ni.2031
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