title: Decoy receptor 3 ameliorates experimental autoimmune encephalomyelitis by directly counteracting local inflammation and downregulating Th17 cells.
abstract: To investigate the therapeutic potential of decoy receptor 3 (DcR3) in multiple sclerosis (MS), we used intrathecal (IT) administration of DcR3 into C57/BL6 mice with experimental autoimmune encephalomyelitis (EAE). DcR3 significantly ameliorated EAE symptoms as shown by a lower clinical score and less inflammation in the spinal cord. The expression of TNF-alpha, IFN-gamma, and IL-17 was lower in the spinal cord in IT DcR3-treated mice. Flow cytometry showed a drastic reduction in IL-17-producing CD4 T cells, slightly fewer IFN-gamma producing CD4 T cells and more IL-4-producing CD4 T cells isolated from the central nervous system (CNS) of IT DcR3-treated mice than of controls. Myelin oligodendrocyte glycoprotein (MOG)-specific T cell proliferation was significantly inhibited in DcR3-treated mice. The IL-17 concentration was lower and the IL-4 concentration higher in the supernatants of MOG-stimulated splenocytes from DcR3-treated mice. An adoptive transfer study showed that splenocytes from DcR3-treated mice retained this disease-inhibiting ability. Our data suggest that DcR3 has potential as a suppressor of CNS inflammation in EAE, which may be attributed to either direct inhibition of CNS inflammation or suppression of encephalitogenic Th17 cells. In conclusion, we demonstrate a therapeutic effect of DcR3 in EAE, suggesting its potential for treating human MS.
authors.affiliation: Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Shyi-Jou
authors.initials: SJ
authors.lastname: Chen
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Wang
authors.forename: Jen-Hsin
authors.initials: JH
authors.lastname: Kao
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Wu
authors.forename: Wen-Tsung
authors.initials: WT
authors.lastname: Lo
authors.forename: Chia-Cho
authors.initials: CC
authors.lastname: Wu
authors.forename: Pao-Luh
authors.initials: PL
authors.lastname: Tao
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Wang
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D007278:Injections, Spinal; D051379:Mice; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D011994:Recombinant Proteins; C505911:TNFRSF6B protein, human