1. Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways
- Author
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Li Guo, Huilian Sun, Xiujuan Song, Jing Zhang, Mo-Yuan Quan, Bin Li, Huiqing Hou, Runjing Cao, and Yafei Sun
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Encephalomyelitis, Autoimmune, Experimental ,Combination therapy ,MAP Kinase Signaling System ,Immunology ,T-Lymphocytes, Regulatory ,03 medical and health sciences ,Mice ,0302 clinical medicine ,immune system diseases ,RAR-related orphan receptor gamma ,Immunology and Allergy ,Medicine ,Animals ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Sirolimus ,Dose-Response Relationship, Drug ,business.industry ,Fingolimod Hydrochloride ,TOR Serine-Threonine Kinases ,Experimental autoimmune encephalomyelitis ,FOXP3 ,medicine.disease ,Fingolimod ,nervous system diseases ,Mice, Inbred C57BL ,030104 developmental biology ,Neurology ,Cancer research ,Th17 Cells ,Drug Therapy, Combination ,Female ,Neurology (clinical) ,business ,Proto-Oncogene Proteins c-akt ,030217 neurology & neurosurgery ,Immunosuppressive Agents ,medicine.drug - Abstract
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-β levels in EAE mice. Combination therapy also modulated IL-17 and TGF-β concentration, RoRγt 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.
- Published
- 2018