? Autoimmune diseases affect almost 10% of the United States population, placing an enormous ? burden on health care systems. Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by immune complex glomerulonephritis, mediated by pathogenic autoantibodies. Our recent studies have demonstrated a profound effect of Fli-1, a member of the Ets transcription factor family, on autoantibody production, disease development and survival in MRL//pr mice, a murine ? autoimmune disease model. Reduced expression of Fli-1 in MRL//pr mice had significantly decreased ? serum levels of total IgG and anti-dsDNA antibodies and markedly increased survival compared with ? littermate wild-type MRL/lpr mice. We recently generated genetically mutant mice with truncated Fli-1 ? protein (Fli-1rec/rec mice). Fli-1rec/rec mice express a truncated Fli1 protein that lacks the carboxy terminal transactivation domain. Fli-1 plays a critical role in the lupus disease development through its effects on the regulating autoreactive B cell development and proliferation. We propose here to investigate the mechanisms in which Fli-1 affects production of autoreactive B cells and the role of Fli-1 in B cell proliferation in MRL//prmice. Our study will provide new insight into disease pathogenesis and understanding the development of autoimmune disease. These new findings will enable development of novel therapeutics that target the specific inflammation pathway ? ? ?
| Mathenia, J; Reyes-Cortes, E; Williams, S et al. (2010) Impact of Fli-1 transcription factor on autoantibody and lupus nephritis in NZM2410 mice. Clin Exp Immunol 162:362-71 |
| Molano, I; Mathenia, J; Ruiz, P et al. (2010) Decreased expression of Fli-1 in bone marrow-derived haematopoietic cells significantly affects disease development in Murphy Roths Large/lymphoproliferation (MRL/lpr) mice. Clin Exp Immunol 160:275-82 |
| Zhang, Xian K; Moussa, Omar; LaRue, Amanda et al. (2008) The transcription factor Fli-1 modulates marginal zone and follicular B cell development in mice. J Immunol 181:1644-54 |
| Bradshaw, Sarah; Zheng, W Jim; Tsoi, Lam C et al. (2008) A role for Fli-1 in B cell proliferation: implications for SLE pathogenesis. Clin Immunol 129:19-30 |
