Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways
Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways
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雷帕霉素和芬戈莫德通过调节 Akt-mTOR 和 MAPK/ERK 通路调节实验性自身免疫性脑脊髓炎中的 Treg/Th17 细胞
DOI：
10.1016/j.jneuroim.2018.08.012
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发表时间：
2018-11-15
影响因子：
3.3
通讯作者：
Song, Xiujuan
中科院分区：
文献类型：
--
作者：
Hou, Huiqing;Cao, Runjing;Song, Xiujuan
雷帕霉素可预防实验性自身免疫性脑脊髓炎（EAE）并激活EAE中的MAPK/ERK通路。因此，我们假设雷帕霉素联合芬戈莫德治疗EAE具有协同作用。我们发现，联合治疗可以改善EAE，并调节EAE小鼠脊髓IL-17和tgf - β水平。联合治疗还可调节脾脏IL-17和tgf - β浓度、RoR γ t和Foxp3 mRNA水平以及Th17细胞和Treg频率。此外，雷帕霉素降低了EAE小鼠的ps6k，增加了pAkt和pERK，而联合治疗下调了pAkt、ps6k和pERK。我们的研究结果为使用这种药物组合治疗EAE提供了见解。
Rapamycin prevents experimental autoimmune encephalomyelitis (EAE) and activates the MAPK/ERK pathway in EAE. Thus, we hypothesized combining rapamycin and fingolimod treatments would have synergistic effects in EAE. We show that combination therapy ameliorated EAE and regulated spinal cord IL-17 and TGF-beta levels in EAE mice. Combination therapy also modulated IL-17 and TGF-beta concentration, RoR gamma t and Foxp3 mRNA levels, and Th17 cell and Treg frequencies in the spleen. Moreover, rapamycin decreased ps6k and increased pAkt and pERK, while combination therapy downregulated pAkt, ps6 k and pERK in EAE mice. Our findings provide insight into using this drug combination to treat EAE.