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

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HighlightsIL-17ko EAMG mice exhibited ablation of MG symptoms.IL-17ko EAMG mice retained AChR at the NMJ and had less AChR specific IgG.Higher levels of Foxp3 and BCL-6 suggest alterations in T cell differentiation.A shift toward Tregs and Tfh cells further implicates an IL-17 independent pathway.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-17ko 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-17ko 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.

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