title: Characterization of the interaction between astrocytes and encephalitogenic lymphocytes during the development of experimental autoimmune encephalitomyelitis (EAE) in mice.
abstract: The nature of pathogenic mechanisms associated with the development of multiple sclerosis (MS) have long been debated. However, limited research was conducted to define the interplay between infiltrating lymphocytes and resident cells of the central nervous system (CNS). Data presented in this report describe a novel role for astrocyte-mediated alterations to myelin oligodendrocyte glycoprotein (MOG)(35-55) -specific lymphocyte responses, elicited during the development of experimental autoimmune encephalitomyelitis (EAE). In-vitro studies demonstrated that astrocytes inhibited the proliferation and interferon (IFN)-γ, interleukin (IL)-4, IL-17 and transforming growth factor (TGF)-β secretion levels of MOG(35-55) -specific lymphocytes, an effect that could be ameliorated by astrocyte IL-27 neutralization. However, when astrocytes were pretreated with IFN-γ, they could promote the proliferation and secretion levels of MOG(35-55) -specific lymphocytes, coinciding with apparent expression of major histocompatibility complex (MHC)-II on astrocytes themselves. Quantitative polymerase chain reaction (qPCR) demonstrated that production of IL-27 in the spinal cord was at its highest during the initial phases. Conversely, production of IFN-γ in the spinal cord was highest during the peak phase. Quantitative analysis of MHC-II expression in the spinal cord showed that there was a positive correlation between MHC-II expression and IFN-γ production. In addition, astrocyte MHC-II expression levels correlated positively with IFN-γ production in the spinal cord. These findings suggested that astrocytes might function as both inhibitors and promoters of EAE. Astrocytes prevented MOG(35-55) -specific lymphocyte function by secreting IL-27 during the initial phases of EAE. Then, in the presence of higher IFN-γ levels in the spinal cord, astrocytes were converted into antigen-presenting cells. This conversion might promote the progression of pathological damage and result in a peak of EAE severity.
authors.affiliation: Department of Neurobiology, Harbin Medical University Provincial Key Lab of Neurobiology, Harbin Medical University, Harbin, China.
authors.forename: J F
authors.initials: JF
authors.lastname: Yang
authors.forename: H Q
authors.initials: HQ
authors.lastname: Tao
authors.forename: Y M
authors.initials: YM
authors.lastname: Liu
authors.forename: X X
authors.initials: XX
authors.lastname: Zhan
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: X Y
authors.initials: XY
authors.lastname: Wang
authors.forename: J H
authors.initials: JH
authors.lastname: Wang
authors.forename: L L
authors.initials: LL
authors.lastname: Mu
authors.forename: L L
authors.initials: LL
authors.lastname: Yang
authors.forename: Z M
authors.initials: ZM
authors.lastname: Gao
authors.forename: Q F
authors.initials: QF
authors.lastname: Kong
authors.forename: G Y
authors.initials: GY
authors.lastname: Wang
authors.forename: J H
authors.initials: JH
authors.lastname: Han
authors.forename: B
authors.initials: B
authors.lastname: Sun
authors.forename: H L
authors.initials: HL
authors.lastname: Li
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005802:Genes, MHC Class II; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000009:adverse effects / Q000276:immunology; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D000939:Epitopes; C486767:Il27 protein, mouse; D007378:Interleukins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma