M Keszei, C Detre, ST Rietdijk, P Muñoz, X Romero, SB Berger, S Calpe, G Liao, W Castro, A Julien, YY Wu, DM Shin, J Sancho, M Zubiaur, HC Morse, L Morel, P Engel, N Wang, C Terhorst. (2011). " A novel isoform of the Ly108 gene ameliorates murine lupus. " J Exp Med. 208, 811-22. PMID: 21422172 DOI: 10.1084/jem.20101653
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.