title: LIGHT (TNFSF14/CD258) is a decisive factor for recovery from experimental autoimmune encephalomyelitis.
abstract: The TNF superfamily ligand LIGHT (lymphotoxin-like, exhibits inducible expression and competes with HSV glycoprotein D for herpesvirus entry mediator [HVEM], a receptor expressed by T lymphocytes) has been shown to play a role in T cell costimulation and be involved in apoptosis of mononuclear cells. As both T cells and monocytes are key components in the development and progression of experimental autoimmune encephalomyelitis (EAE), we studied the role of LIGHT in EAE. Following immunization with myelin oligodendrocyte glycoprotein peptide (35-55), LIGHT-deficient mice developed severe EAE that resulted in an atypically high mortality rate. Histological examinations revealed intensive activation of microglia/macrophages in the CNS and higher numbers of apoptotic cells within the CNS parenchyma of LIGHT-deficient mice. However, myelin oligodendrocyte glycoprotein peptide-specific CD4(+) T cells from LIGHT-deficient mice showed reduced IFN-γ and IL-17 production and migration. Serum levels of reactive nitrogen intermediates and CNS transcripts of several proinflammatory cytokines and chemokines were also substantially decreased in the absence of LIGHT. EAE adoptive transfer experiments and bone marrow chimeras indicated that expression of LIGHT on donor cells is not required for disease induction. However, its expression on CNS host cells is a decisive factor to limit disease progression and tissue damage. Together, these data show that LIGHT expression is crucially involved in controlling activated macrophages/microglia during autoimmune CNS inflammation.
authors.affiliation: Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Paula
authors.initials: P
authors.lastname: Maña
authors.forename: David
authors.initials: D
authors.lastname: Liñares
authors.forename: Diego G
authors.initials: DG
authors.lastname: Silva
authors.forename: Susan
authors.initials: S
authors.lastname: Fordham
authors.forename: Stefanie
authors.initials: S
authors.lastname: Scheu
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Maria
authors.initials: M
authors.lastname: Staykova
authors.forename: Edward M
authors.initials: EM
authors.lastname: Bertram
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020127:Recovery of Function / Q000235:genetics / Q000276:immunology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000172:deficiency / Q000502:physiology*
chemical_list: C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14