The immunosuppressant fingolimod ameliorates experimental autoimmune myasthenia gravis by regulating T-cell balance and cytokine secretion

Myasthenia gravis is an autoimmune disease that affects skeletal muscle strength by impeding communication within the neuromuscular junction (NMJ). Research has shown that sphingosine-1-phosphate (S1P)/S1P receptor signaling may be involved in the process of neuromuscular diseases. Fingolimod is structurally similar to S1P, whose immunosuppressive effect has been recognized in many immune diseases. However, the mechanism underlying fingolimod's action on experimental autoimmune myasthenia gravis is still far from clear. The aim of this study was to investigate the efficacy and possible mechanism of fingolimod on experimental autoimmune myasthenia gravis. Our results showed that pretreatment with fingolimod improved experimental autoimmune myasthenia gravis symptoms in a dose-dependent manner, including decreased anti-acetylcholine receptor-2α autoantibody titer, reduced compound muscle action potential decrement, and increased acetylcholine receptor content. Further investigation indicated that fingolimod inhibited lymphocyte proliferation responses and also regulated the balance of Th1/Th2 cells and Treg/Th17 cells. Moreover, fingolimod suppressed the secretion of pro-inflammatory or inflammatory cytokines IL-17A, IL-6, and INF-γ, but did not noticeably alter the secretion of immunosuppressive cytokines TGF-β1 and IL-4. In conclusion, our results suggest that fingolimod has a preventive effect on experimental autoimmune myasthenia gravis by interfering with lymphocyte function.