A novel isoform of the Ly108 gene ameliorates murine lupus

Marton Keszei, Cynthia Detre, Svend T. Rietdijk, Pilar Muñoz, Xavier Romero, Scott B. Berger, Silvia Calpe, Gongxian Liao, Wilson Castro, Aimee Julien, Ying Yu Wu, Dong Mi Shin, Jaime Sancho, Mercedes Zubiaur, Herbert C. Morse, Laurence Morel, Pablo Engel, Ninghai Wang, Cox Terhorst

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46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)811-822
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number4
DOIs
StatePublished - Apr 11 2011
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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