Ablation of IL-17 expression moderates experimental autoimmune myasthenia gravis disease severity.

An array of cytokines influences the pathogenesis of early onset myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG). Patients with MG, in particular those with more severe weakness, have elevations of the pro-inflammatory cytokine IL-17 in the blood. We assessed the role of IL-17A in autoimmunity by inducing EAMG in mice with knockout of IL-17 and found a reduction of EAMG severity, but not a complete ablation of disease. The IL-17 mice had no evidence of weakness, low levels of acetylcholine receptor antibodies, and retention of acetylcholine receptor at the neuromuscular junction. Splenic germinal center size was reduced in EAMG IL-17 mice along with elevations of Foxp3 and BCL-6 gene expression, suggesting a shift away from pro-inflammatory signals. The results emphasize the importance of IL-17 in EAMG development and that IL-17 independent pathways drive the autoimmune reaction.