title: Development of experimental autoimmune encephalomyelitis critically depends on CD137 ligand signaling.
abstract: Multiple sclerosis (MS) is a degenerative autoimmune disease of the CNS. Experimental autoimmune encephalomyelitis (EAE) is a commonly used murine model for MS. Here we report that CD137 ligand (CD137L, 4-1BB ligand, TNFS9), a member of the TNF superfamily, is critical for the development of EAE. EAE symptoms were significantly ameliorated in CD137L(-/-) mice. In the absence of CD137L, myelin oligodendrocyte glycoprotein (MOG)-specific T-cells secreted lower levels of T(h)1/T(h)17 cell-associated cytokines. MOG-specific T-cells also trafficked less efficiently to the CNS in CD137L(-/-) mice, possibly as a consequence of reduced expression of vascular cell adhesion molecule-1 (VCAM-1), which regulates leukocyte extravasation. Thus, CD137L regulates many functions of MOG-specific T-cells that contribute to EAE and may represent a novel therapeutic target for the treatment of MS.
authors.affiliation: Departments of Microbiology and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Martínez Gómez
authors.forename: J Ludovic
authors.initials: JL
authors.lastname: Croxford
authors.forename: Kim Pin
authors.initials: KP
authors.lastname: Yeo
authors.forename: Véronique
authors.initials: V
authors.lastname: Angeli
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwarz
authors.forename: Stephan
authors.initials: S
authors.lastname: Gasser
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9