TY - JOUR
T1 - CXCR4/CXCL12 hyperexpression plays a pivotal role in the pathogenesis of lupus
AU - Wang, Andrew
AU - Fairhurst, Anna Marie
AU - Tus, Katalin
AU - Subramanian, Srividya
AU - Liu, Yang
AU - Lin, Fangming
AU - Igarashi, Peter
AU - Zhou, Xin J.
AU - Batteux, Frederic
AU - Wong, Donald
AU - Wakeland, Edward K.
AU - Mohan, Chandra
PY - 2009/4/1
Y1 - 2009/4/1
N2 - 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.
AB - 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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U2 - 10.4049/jimmunol.0801920
DO - 10.4049/jimmunol.0801920
M3 - Article
C2 - 19299746
AN - SCOPUS:64249134814
SN - 0022-1767
VL - 182
SP - 4448
EP - 4458
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -