The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF

M El-Behi, B Ciric, H Dai, Y Yan, M Cullimore… - Nature …, 2011 - nature.com
M El-Behi, B Ciric, H Dai, Y Yan, M Cullimore, F Safavi, GX Zhang, BN Dittel, A Rostami
Nature immunology, 2011nature.com
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 …
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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