Fli-1 transcription factor is involved in cytokine production in spleen cells upon Toll-like receptor stimulation (P1218)

Abstract

Friend leukemia integration-1, a member of the Ets family of transcription factors, is highly expressed in splenocytes. Dysregulation of Fli-1 occurs in Systemic Lupus Erythematosus patients and lupus prone mice. Systemic Lupus Erythematosus is an autoimmune disease utilizing the innate and adaptive immune response. Reduction of Fli-1 expression in NZM 2410 and MRL/lpr lupus prone murine models resulted in decreased severity of disease. Studies of Toll-like receptor 7 and 8 reveal various implications in autoimmunity. Inflammatory cytokine IL-6 plays a pivotal role in the pathogenesis of SLE. The role of Fli-1 in Toll-like receptor signaling pathways in splenocytes is unknown. In this study, we generated Fli-1 heterozygous knockout (Fli-1+/-) B6 mice that expressed decreased levels of Fli-1 and investigated the impact of Fli-1 on splenocyte development and cytokine production. Spleen cells were isolated from Fli-1+/- B6 mice and wild-type controls. Examination of cell populations in the spleen revealed unaffected populations of B, T, Natural Killers and Dendritic cells between Fli1+/- mice and wild-type littermates. Spleen cells isolated from Fli-1+/- mice produced increased levels of IL-6 compared to wild-type mice upon stimulation with Toll-like receptor 7 ligand R848. Our results suggest that Fli-1 is involved in IL-6 cytokine production in spleen cells.