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.

中文翻译：

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转录因子ROR-γ的抑制可降低乙酰胆碱受体抗体阳性重症肌无力中的致病性Th17细胞。

重症肌无力（MG）患者中，随着疾病严重程度的增加，产生IL-17的CD4 T细胞（Th17）细胞显着增加。为了抑制Th17细胞的产生，我们检查了抑制视黄酸受体相关的孤儿受体C（RORγ）的作用，R17是对分化至关重要的Th17特异性转录因子。RORγ抑制作用极大地降低了Th17细胞的频率，包括共同产生IFN-γ和IL-17的致病性Th17细胞。其他T辅助者子集不受影响。同时，MG患者中产生IL-17和IL-17 /IFN-γ的CD8 T细胞亚群增加，并受到RORγ抑制剂的抑制。这些发现为探索靶向Th17疗法（包括ROR-γ抑制剂）以治疗MG患者提供了理论依据。