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- Title
The encephalitogenicity of T<sub>H</sub>17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF.
- Authors
El-Behi, Mohamed; Ciric, Bogoljub; Dai, Hong; Yan, Yaping; Cullimore, Melissa; Safavi, Farinaz; Zhang, Guang-Xian; Dittel, Bonnie N; Rostami, Abdolmohamad
- 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.
- Publication
Nature Immunology, 2011, Vol 12, Issue 6, p568
- ISSN
1529-2908
- Publication type
Academic Journal
- DOI
10.1038/ni.2031