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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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.
The authors declare no competing financial interests.
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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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