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PLoS One. 2014 Mar 17;9(3):e92054. doi: 10.1371/journal.pone.0092054. eCollection 2014.

Reduced B lymphoid kinase (Blk) expression enhances proinflammatory cytokine production and induces nephrosis in C57BL/6-lpr/lpr mice.

Author information

1
Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, New York, United States of America.
2
Department of Pathology, State University of New York Upstate Medical University, Syracuse, New York, United States of America.

Abstract

BLK, which encodes B lymphoid kinase, was recently identified in genome wide association studies as a susceptibility gene for systemic lupus erythematosus (SLE), and risk alleles mapping to the BLK locus result in reduced gene expression. To determine whether BLK is indeed a bona fide susceptibility gene, we developed an experimental mouse model, namely the Blk+/-.lpr/lpr (Blk+/-.lpr) mouse, in which Blk expression levels are reduced to levels comparable to those in individuals carrying a risk allele. Here, we report that Blk is expressed not only in B cells, but also in IL-17-producing γδ and DN αβ T cells and in plasmacytoid dendritic cells (pDCs). Moreover, we found that solely reducing Blk expression in C57BL/6-lpr/lpr mice enhanced proinflammatory cytokine production and accelerated the onset of lymphoproliferation, proteinuria, and kidney disease. Together, these findings suggest that BLK risk alleles confer susceptibility to SLE through the dysregulation of a proinflammatory cytokine network.

PMID:
24637841
PMCID:
PMC3956874
DOI:
10.1371/journal.pone.0092054
[Indexed for MEDLINE]
Free PMC Article
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