Targeting the CXCR4/CXCL12 axis in systemic lupus erythematosus.
BACKGROUND
CXCR4 antagonists have garnered much interest as promising treatments for cancer metastases and HIV. Given its ability to attract multiple leukocyte subsets and stimulate B cell production and myelopoeisis, recent attention has been directed to these inhibitors in the treatment of autoimmune diseases, such as systemic lupus erythematosus (SLE).


OBJECTIVE
To assess the potential of CXCR4 antagonists in SLE.


METHODS
We reviewed literature on the expression of CXCR4 and its ligand CXCL12, and the effects of CXCR4 antagonists in murine and human SLE.


CONCLUSIONS
CXCR4 and CXCL12 have been found at abundant levels in peripheral blood leukocyte subsets as well as immune and non-immune organs in lupus-prone murine models. While SLE patients have displayed upregulated, downregulated, or unchanged levels of CXCR4 in circulating blood lymphocytes, CXCR4 and CXCL12 were found prominently in the skin and kidney, suggesting that the ultimate destinations of CXCR4(+) cells include these areas. CXCR4 antagonists have been explored in murine lupus models, in which disease severity and nephritis significantly improved. While clinical trials of CXCR4 antagonists in SLE have yet to be initiated, these inhibitors appear to have the potential to improve disease prognosis in severe lupus patients, particularly those with lupus nephritis.
Chong
Benjamin F
BF
University of Texas Southwestern Medical Center, Department of Internal Medicine/Rheumatology, Mail Code 8884, Y8.204, 5323 Harry Hines Boulevard, Dallas, TX 75390-8884, USA.
Mohan
Chandra
C
D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D007166:Immunosuppressive Agents; D019718:Receptors, CXCR4