The Friend leukaemia virus integration 1 (Fli-1) transcription factor affects lupus nephritis development by regulating inflammatory cell infiltration into the kidney

Clin Exp Immunol. 2014 Jul;177(1):102-9. doi: 10.1111/cei.12310.


The transcription factor Friend leukaemia virus integration 1 (Fli-1) is implicated in the pathogenesis of systemic lupus erythematosus in both human patients and murine models of lupus. Murphy Roths large (MRL)/lpr mice and New Zealand mixed (NZM)2410 mice, murine models of lupus, with decreased expression of Fli-1 had significantly prolonged survival and reduced nephritis. Lupus nephritis is a major cause of mortality and morbidity in patients, and inflammatory cell infiltration plays a key role in the development of the disease. To study how the expression of Fli-1 affects the infiltration of inflammatory cells into the kidneys, we generated congenic enhanced green fluorescent protein (GFP) transgenic MRL/lpr mice. A significantly increased number of GFP-expressing inflammatory cells infiltrated the kidneys of wild-type MRL/lpr mice compared to Fli-1 heterozygous (Fli-1(+/-)) MRL/lpr mice after injection of GFP(+) cells. Expression of inflammatory chemokine mRNA, including chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4 and CCL5, was significantly lower in the kidneys from Fli-1(+/-) MRL/lpr mice compared to wild-type littermates. Numbers of infiltrated cells into the kidneys correlate with expression levels of CCL2, CCL4 and CCL5, but not the titres of anti-dsDNA autoantibodies in these mice. Significantly increased inflammatory cells from wild-type MRL/lpr mice infiltrated into kidneys compared to the cells from Fli-1(+/-) MRL/lpr mice. The chemotaxis of inflammatory cells from Fli-1(+/-) MRL/lpr mice towards each chemokine was decreased significantly compared to inflammatory cells from wild-type MRL/lpr mice in the transwell migration assay in vitro. Our results indicate that Fli-1 affects lupus nephritis development by regulating the expression of chemokines in the kidney and the migration of inflammatory cells.

Keywords: Fli-1; chemokines; chemotaxis; infiltration; lupus nephritis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cells, Cultured
  • Chemokines / genetics
  • Chemokines / metabolism
  • Chemotaxis* / genetics
  • Disease Models, Animal
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Green Fluorescent Proteins / genetics
  • Humans
  • Immunotherapy*
  • Inflammation / genetics
  • Kidney / immunology*
  • Kidney / pathology
  • Lupus Nephritis / genetics
  • Lupus Nephritis / immunology*
  • Mice
  • Mice, Inbred MRL lpr
  • Mice, Transgenic
  • Proto-Oncogene Protein c-fli-1 / genetics
  • Proto-Oncogene Protein c-fli-1 / metabolism*


  • Chemokines
  • Proto-Oncogene Protein c-fli-1
  • Green Fluorescent Proteins