Rapamycin alleviates inflammation and muscle weakness, while altering the Treg/Th17 balance in a rat model of myasthenia gravis.

Feng Jing,Xusheng Huang,Fang Cui,Fei Yang,Li Ling,Zhaohui Chen

doi:10.1042/bsr20170767

Abstract

Myasthenia gravis (MG) is an autoimmune disease commonly treated with immunosuppressants. We evaluated the novel immunosuppressant, rapamycin (RAPA), in a rat model of experimental autoimmune MG (EAMG). Mortality rates in the RAPA (12%) were significantly down compared with the EAMG (88%) or cyclophosphamide (CTX) (68%) intervention groups. Muscular weakness decreased after both RAPA and CTX treatment. However, Lennon scores were lower (1.74 ± 0.49, 3.39 ± 0.21, and 3.81 ± 0.22 in RAPA, CTX, and EAMG groups, respectively), and body weights (203.12 ± 4.13 g, 179.23 ± 2.13 g, and 180.13 ± 5.13 g in RAPA, CTX, and EAMG groups, respectively) were significantly higher, only in the RAPA group. The proportion of regulatory T cells (Treg) significantly increased, while that of Th17 cells significantly decreased in the RAPA group compared with the EAMG group. In comparison, CTX intervention resulted in increased Th17 but significantly decreased Tregs. Hence, RAPA can be more effectively used in comparison with CTX to treat MG, with an efficacy higher than that of CTX. In addition, our results suggest RAPA’s efficacy in alleviating symptoms of MG stems from its ability to correct the Treg/Th17 imbalance observed in MG.

Highlights

Myasthenia gravis (MG) is a T-cell-dependent and B-cell-mediated autoimmune disease, which is pathologically characterized by a neuromuscular transmission disorder resulting from damage in acetylcholine receptors (AChRs) on the post-synaptic membrane [1]
Reduction in the number of regulatory T cell (Treg) cells may increase the risk of autoimmune diseases, and studies indicated that the number of Treg cells is reduced in MG pathogenesis [4,5]
The Lennon scores of the animals in the experimental autoimmune MG (EAMG) group increased gradually (Figure 1A) and body weights declined over time (Figure 1B)

Summary

Introduction

Myasthenia gravis (MG) is a T-cell-dependent and B-cell-mediated autoimmune disease, which is pathologically characterized by a neuromuscular transmission disorder resulting from damage in acetylcholine receptors (AChRs) on the post-synaptic membrane [1]. Treg cells play an important role in maintaining immune tolerance and balance [3]. Reduction in the number of Treg cells may increase the risk of autoimmune diseases, and studies indicated that the number of Treg cells is reduced in MG pathogenesis [4,5]. Th17 cells play a pivotal role in mediating inflammatory reactions and promoting autoimmune reactions [6]. Patients with MG have been shown to have an increased population of Th17 cells [7]. This indicates that a Treg/Th17 imbalance (low Treg and high Th17 T-cell subsets) may be involved in the pathogenesis of MG

Methods

Results

Discussion

Conclusion