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

Andrew Wang, Anna Marie Fairhurst, Katalin Tus, Srividya Subramanian, Yang Liu, Fangming Lin, Peter Igarashi, Xin J. Zhou, Frederic Batteux, Donald Wong, Edward K. Wakeland, Chandra Mohan

Research output: Contribution to journalArticle

84 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4448-4458
Number of pages11
JournalJournal of Immunology
Volume182
Issue number7
DOIs
StatePublished - Apr 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wang, A., Fairhurst, A. M., Tus, K., Subramanian, S., Liu, Y., Lin, F., Igarashi, P., Zhou, X. J., Batteux, F., Wong, D., Wakeland, E. K., & Mohan, C. (2009). CXCR4/CXCL12 hyperexpression plays a pivotal role in the pathogenesis of lupus. Journal of Immunology, 182(7), 4448-4458. https://doi.org/10.4049/jimmunol.0801920