ROR[gamma]t drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation

• Published in: Nature immunology Vol. 12; no. 6; p. 560
• Main Authors: Codarri, Laura, Gyülvészi, Gabor, Tosevski, Vinko, Hesske, Lysann, Fontana, Adriano, Magnenat, Laurent, Suter, Tobias, Becher, Burkhard
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group 01.06.2011
• Subjects: Central nervous system
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.2027

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 RORγt drove expression of the cytokine GM-CSF in helper T cells, whereas IL-12, interferon-γ (IFN-γ) 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-γ, 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.