CXCR4/CXCL12 hyperexpression plays a pivotal role in the pathogenesis of lupus

A Wang, AM Fairhurst, K Tus… - The Journal of …, 2009 - journals.aai.org
A Wang, AM Fairhurst, K Tus, S Subramanian, Y Liu, F Lin, P Igarashi, XJ Zhou, F Batteux…
The Journal of Immunology, 2009journals.aai.org
Among various surface molecules screened, CXCR4 was significantly up-regulated on
monocytes, neutrophils, B cell subsets, and plasma cells in multiple murine models of lupus
with active nephritis, including B6. Sle1Yaa, BXSB, and MRL. lpr. TLR-mediated signaling
and inflammatory cytokines accounted in part for this increase. Increased CXCR4
expression was associated with functional consequences, including increased migration
and enhanced B cell survival. Simultaneously, the ligand for CXCR4, CXCL12, was …
Abstract
Among various surface molecules screened, CXCR4 was significantly up-regulated on monocytes, neutrophils, B cell subsets, and plasma cells in multiple murine models of lupus with active nephritis, including B6. Sle1Yaa, BXSB, and MRL. lpr. TLR-mediated signaling and inflammatory cytokines accounted in part for this increase. Increased CXCR4 expression was associated with functional consequences, including increased migration and enhanced B cell survival. Simultaneously, the ligand for CXCR4, CXCL12, was significantly up-regulated in the nephritic kidneys. Treatment with a peptide antagonist of CXCR4 prolonged survival and reduced serum autoantibodies, splenomegaly, intrarenal leukocyte trafficking, and end organ disease in a murine model of lupus. These findings underscore the pathogenic role of CXCR4/CXCL12 in lymphoproliferative lupus and lupus nephritis and highlight this axis as a promising therapeutic target in this disease.
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