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Inhibition of the transcription factor ROR-γ reduces pathogenic Th17 cells in acetylcholine receptor antibody positive myasthenia gravis

Yi, John and Russo, Melissa and Raja, Shruti and Massey, Janice and Juel, Vern and Shin, Jay and Hobson-Webb, Lisa and Gable, Karissa and Guptill, Jeffrey (2020) Inhibition of the transcription factor ROR-γ reduces pathogenic Th17 cells in acetylcholine receptor antibody positive myasthenia gravis. Experimental Neurology, 325 (March ). pp. 1-8. ISSN 0014-4886

Abstract

IL-17 producing CD4 T cells (Th17) cells increase significantly with disease severity in myasthenia gravis (MG) patients. To suppress the generation of Th17 cells, we examined the effect of inhibiting retinoic acid receptor-related-orphan-receptor-C (RORγ), a Th17-specific transcription factor critical for differentiation. RORγ inhibition profoundly reduced Th17 cell frequencies, including IFN-γ and IL-17 co-producing pathogenic Th17 cells. Other T helper subsets were not affected. In parallel, CD8 T cell subsets producing IL-17 and IL-17/IFN-γ were increased in MG patients and inhibited by the RORγ inhibitor. These findings provide rationale for exploration of targeted Th17 therapies, including ROR-γ inhibitors, to treat MG patients.

Item Type: Article
Keywords: AChR IL-17 Interferon-gamma Myasthenia gravis Receptor-related orphan receptor gamma Th17 cell
Date Deposited: 25 Jan 2020 00:45
Last Modified: 25 Jan 2020 00:45
URI: https://oak.novartis.com/id/eprint/40491

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