Cutting Edge: The Pathogenicity of IFN-g–Producing Th17 Cells Is Independent of T-bet

Cutting Edge: The Pathogenicity of IFN-g–Producing Th17 Cells Is Independent of T-bet

Abstract

During the development of experimental autoimmune encephalomyelitis (EAE), the proportion of pathogenic and myelin-specific cells within CNS-infiltrating cytokine-producing Th cells is unknown. Using an IL-17A/IFN-γ double reporter mouse and I-Ab/myelin oligodendrocyte glycoprotein 38–49 tetramer, we show in this study that IL-17+IFN-γ+ Th cells, which are expanded in the CNS during EAE, are highly enriched in myelin oligodendrocyte glycoprotein–specific T cells. We further demonstrate that IL-23 is essential for the generation and expansion of IFN-γ–producing Th17 cells independently of the Th1-associated transcription factors T-bet, STAT1, and STAT4. Furthermore, Th17 and IL-17+IFN-γ+ Th cells can induce CNS autoimmunity independently of T-bet. Whereas T-bet is crucial for Th1-mediated EAE, it is dispensable for Th17 cell–mediated autoimmunity. Our results suggest the existence of different epigenetic programs that regulate IFN-γ expression in Th1 and Th17 cells.

Authors: Rebekka Duhen, Simon Glatigny, Carlos A. Arbelaez, Tiffany C. Blair, Mohamed Oukka and Estelle Bettelli

Influence Factor: 4.8559

Citation: The Journal of Immunology 190, 4478 (2013).

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