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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Yi, JS; Russo, MA; Raja, S; Massey, JM; Juel, VC; Shin, J; Hobson-Webb, LD; Gable, K; Guptill, JT

Published Date

  • March 2020

Published In

Volume / Issue

  • 325 /

Start / End Page

  • 113146 -

PubMed ID

  • 31838097

Pubmed Central ID

  • 31838097

Electronic International Standard Serial Number (EISSN)

  • 1090-2430

Digital Object Identifier (DOI)

  • 10.1016/j.expneurol.2019.113146

Language

  • eng

Conference Location

  • United States