title: Metformin ameliorates the development of experimental autoimmune encephalomyelitis by regulating T helper 17 and regulatory T cells in mice.
abstract: Immoderate immunoreaction of antigen-specific Th17 and Treg cell dysfunction play critical roles in the pathogenesis of multiple sclerosis. We examined Th17/Treg immune responses and the underlying mechanisms in response to metformin in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE). Metformin reduced Th17 and increased Treg cell percentages along with the levels of associated cytokines. Molecules involved in cellular metabolism were altered in mice with EAE. Suppressed activation of mTOR and its downstream target, HIF-1α, likely mediated the protective effects of metformin. Our findings demonstrate that regulation of T cell metabolism represents a new therapeutic target for CNS autoimmune disorders.
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of neurosurgery, Affiliated Hospital of Chengde Medical College, Chengde, 06700, Hebei, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Neurology, Affiliated Hospital of Hebei University, Baoding, 071000, Hebei, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China; Key Laboratory of Hebei Neurology, Shijiazhuang, 050000, Hebei, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Runjing
authors.initials: R
authors.lastname: Cao
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China; Key Laboratory of Hebei Neurology, Shijiazhuang, 050000, Hebei, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
authors.forename: Moyuan
authors.initials: M
authors.lastname: Quan
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China; Key Laboratory of Hebei Neurology, Shijiazhuang, 050000, Hebei, China. Electronic address: guoli6@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000009:adverse effects / Q000276:immunology; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; C497443:Hif1a protein, mouse; D007004:Hypoglycemic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; C445081:myelin oligodendrocyte glycoprotein (35-55); D008687:Metformin
keywords: AMPK/mTOR; Experimental autoimmune encephalomyelitis; Metformin; Multiple sclerosis; Th17 cells; Treg cells