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J Exp Med. 2011 Apr 11;208(4):811-22. doi: 10.1084/jem.20101653. Epub 2011 Mar 21.

A novel isoform of the Ly108 gene ameliorates murine lupus.

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1
Division of Immunology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. mkeszei@bidmc.harvard.edu

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.

PMID:
21422172
PMCID:
PMC3135348
DOI:
10.1084/jem.20101653
[Indexed for MEDLINE]
Free PMC Article
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