Systemic Lupus erythematosus (SLE) is an autoimmune disease caused, in part, by 
abnormalities in cells of the immune system including B and T cells. Genetically 
reducing globally the expression of the ETS transcription factor FLI1 by 50% in 
two lupus mouse models significantly improves disease measures and survival 
through an unknown mechanism. In this study we analyze the effects of reducing 
FLI1 in the MRL/lpr lupus prone model on T cell function. We demonstrate that 
adoptive transfer of MRL/lpr Fli1(+/+) or Fli1(+/-) T cells and B cells into 
Rag1-deficient mice results in significantly decreased serum immunoglobulin 
levels in animals receiving Fli1(+/-) lupus T cells compared to animals 
receiving Fli1(+/+) lupus T cells regardless of the genotype of co-transferred 
lupus B cells. Ex vivo analyses of MRL/lpr T cells demonstrated that Fli1(+/-) T 
cells produce significantly less IL-4 during early and late disease and 
exhibited significantly decreased TCR-specific activation during early disease 
compared to Fli1(+/+) T cells. Moreover, the Fli1(+/-) T cells expressed 
significantly less neuraminidase 1 (Neu1) message and decreased NEU activity 
during early disease and significantly decreased levels of glycosphingolipids 
during late disease compared to Fli1(+/+) T cells. FLI1 dose-dependently 
activated the Neu1 promoter in mouse and human T cell lines. Together, our 
results suggest reducing FLI1 in lupus decreases the pathogenicity of T cells by 
decreasing TCR-specific activation and IL-4 production in part through the 
modulation of glycosphingolipid metabolism. Reducing the expression of FLI1 or 
targeting the glycosphingolipid metabolic pathway in lupus may serve as a 
therapeutic approach to treating lupus.