title: A novel isoform of the Ly108 gene ameliorates murine lupus.
abstract: Studies of human systemic lupus erythematosus patients and of murine congenic mouse strains associate genes in a DNA segment on chromosome 1 with a genetic predisposition for this disease. The systematic analysis of lupus-prone congenic mouse strains suggests a role for two isoforms of the Ly108 receptor in the pathogenesis of the disease. In this study, we demonstrate that Ly108 is involved in the pathogenesis of lupus-related autoimmunity in mice. More importantly, we identified a third protein isoform, Ly108-H1, which is absent in two lupus-prone congenic animals. Introduction of an Ly108-H1-expressing transgene markedly diminishes T cell-dependent autoimmunity in congenic B6.Sle1b mice. Thus, an immune response-suppressing isoform of Ly108 can regulate the pathogenesis of lupus.
authors.affiliation: Division of Immunology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. mkeszei@bidmc.harvard.edu
authors.forename: Marton
authors.initials: M
authors.lastname: Keszei
authors.forename: Cynthia
authors.initials: C
authors.lastname: Detre
authors.forename: Svend T
authors.initials: ST
authors.lastname: Rietdijk
authors.forename: Pilar
authors.initials: P
authors.lastname: Muñoz
authors.forename: Xavier
authors.initials: X
authors.lastname: Romero
authors.forename: Scott B
authors.initials: SB
authors.lastname: Berger
authors.forename: Silvia
authors.initials: S
authors.lastname: Calpe
authors.forename: Gongxian
authors.initials: G
authors.lastname: Liao
authors.forename: Wilson
authors.initials: W
authors.lastname: Castro
authors.forename: Aimee
authors.initials: A
authors.lastname: Julien
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Wu
authors.forename: Dong-Mi
authors.initials: DM
authors.lastname: Shin
authors.forename: Jaime
authors.initials: J
authors.lastname: Sancho
authors.forename: Mercedes
authors.initials: M
authors.lastname: Zubiaur
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
authors.forename: Pablo
authors.initials: P
authors.lastname: Engel
authors.forename: Ninghai
authors.initials: N
authors.lastname: Wang
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D015551:Autoimmunity; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005091:Exons; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D000950:Antigens, Ly; D020033:Protein Isoforms; C000604063:Slamf6 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family