Open AccessCXCR4/CXCL12 Hyperexpression Plays a Pivotal Role in the Pathogenesis of Lupus
Author(s) -
Andrew Wang,
AnnaMarie Fairhurst,
Katalin Tus,
Srividya Subramanian,
Yang Liu,
Fangming Lin,
Peter Igarashi,
Xin J. Zhou,
Frédéric Batteux,
Donald Wong,
Edward K. Wakeland,
Chandra Mohan
Publication year - 2009
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.0801920
Subject(s) - lupus nephritis , systemic lupus erythematosus , cxcr4 , pathogenesis , immunology , autoantibody , chemokine , receptor , medicine , inflammation , biology , disease , antibody
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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