Journal
NATURE IMMUNOLOGY
Volume 12, Issue 6, Pages 560-U248Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2027
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Funding
- Swiss National Science Foundation [31003AB.131091]
- Swiss Multiple Sclerosis Society
- Koetser Foundation
- Merck-Serono-Geneva
- Forschungskredit of the University of Zurich
- Gemeinnutzige Hertie-Stiftung
- Swiss National Science Foundation (SNF) [31003AB_131091] Funding Source: Swiss National Science Foundation (SNF)
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Although the role of the T(H)1 and T(H)17 subsets of helper T cells as disease mediators in autoimmune neuroinflammation remains a subject of some debate, none of their signature cytokines are essential for disease development. Here we report that interleukin 23 (IL-23) and the transcription factor ROR gamma t drove expression of the cytokine GM-CSF in helper T cells, whereas IL-12, interferon-gamma (IFN-gamma) and IL-27 acted as negative regulators. Autoreactive helper T cells specifically lacking GM-CSF failed to initiate neuroinflammation despite expression of IL-17A or IFN-gamma, whereas GM-CSF secretion by Ifng(-/-)Il17a(-/-)helper T cells was sufficient to induce experimental autoimmune encephalomyelitis (EAE). During the disease effector phase, GM-CSF sustained neuroinflammation via myeloid cells that infiltrated the central nervous system. Thus, in contrast to all other known helper T cell-derived cytokines, GM-CSF serves a nonredundant function in the initiation of autoimmune inflammation regardless of helper T cell polarization.
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