Objective: Investigation of the role of IL-27/IL-27Rα (WSX-1) in the development of autoimmune disorders in MRL/lpr mouse, which is considered as an experimental model of systemic lupus erythematosus in humans.
Methods: We generated two strains of WSX-1 transgenic mice in the MRL/lpr background (WSX-1 Tg High MRL/lpr mice and WSX-1Tg Low MRL/lpr mice) with different expression levels of WSX-1, and investigated the effect of WSX-1 overexpression on survival, glomerulonephritis, and immunological properties.
Results: In comparison with wild-type MRL/lpr(WT) and Tg Low (TgL) mice, Tg High(TgH) mice exhibited a prolonged lifespan and no apparent development of autoimmune nephritis. Production of anti-dsDNA antibody and total IgG and IgG2a were significantly lower in TgH mice than those of TgL and WT mice. The expressed amounts of IFN-γ and IL-4 mRNA by CD4+ T cells from Tg mice decreased in a dose-dependent fashion. CD4+ splenic lymphocytes in TgH mice were more subject to the IL-27-mediated suppression of cytokine production. In vitro stimulation of CD4+ T cells by IL-27 resulted in over phosphorylation of STAT3 in TgH cells than in WT cells.
Conclusion: WSX-1 over-expression in the MRL/lpr background rendered the autoimmune prone mice protected from the development of autoimmune diseases.Our results suggest that IL-27 signal may be a therapeutic target against autoimmune diseases including human SLE.
- MRL/lpr mice
- autoimmune disease