Codarri, L; Gyülvészi, G; Tosevski, V; Hesske, L; Fontana, A; Magnenat, L; Suter, T; Becher, B (2011). RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nature Immunology, 12(6):560-567.
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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 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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology|
04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||09 Feb 2012 14:46|
|Last Modified:||27 Nov 2013 17:19|
|Publisher:||Nature Publishing Group|
|ISSN:||1529-2908 (P) 1529-2916 (E)|
|Citations:||Web of Science®. Times cited: 136|
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