The encephalitogenicity of TH 17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF

Mohamed El-Behi, Bogoljub Ciric, Hong Dai, Yaping Yan, Melissa Cullimore, Farinaz Safavi, Guang Xian Zhang, Bonnie N. Dittel, Abdolmohamad Rostami

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666 Scopus citations

Abstract

Interleukin 17 (IL-17)-producing helper T cells (TH 17 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 TH 17 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 TH 17 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 T H 17 cells as a crucial source of GM-CSF in autoimmune inflammation.

Original languageEnglish (US)
Pages (from-to)568-575
Number of pages8
JournalNature Immunology
Volume12
Issue number6
DOIs
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    El-Behi, M., Ciric, B., Dai, H., Yan, Y., Cullimore, M., Safavi, F., Zhang, G. X., Dittel, B. N., & Rostami, A. (2011). The encephalitogenicity of TH 17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nature Immunology, 12(6), 568-575. https://doi.org/10.1038/ni.2031