B7-2 gene silencing by lentivirus-mediated delivery of shRNA reduces progression of experimental lupus nephritis

Over-activation of B7/CD28 co-stimulatory signal is believed to play an important role in promoting hyperfunctional immune response which contributes to autoimmune diseases. In the present study, we generated the recombinant lentivirus transcribing short hairpin RNA (shRNA) specific for mouse B7-2 gene silencing and B7/CD28 signal inhibition to explore and evaluate a potential candidate approach to suppress B7/CD28 co-signal and ameliorate auto-immune diseases. A pristine-induced mouse model of lupus nephritis (LN) was generated to assess the effects of an immune intervention on the progression of systemic lupus erythematosus (SLE) and end-stage renal injury. Lentivirus-mediated B7-2 gene silencing attenuated the over-activity of splenic immune cells, including macrophages, dendritic cells, granulocytes, and B-cells in the experimental lupus nephritis model ten days after pristane was given. Production of auto-antibodies, e.g., antinuclear antibody (ANA), anti-double-strand-DNA antibody (antidsDNA), and development of proteinuria after treatment with B7-2 silencing lentivirus were lessened from the third or fourth month while auto-antibodies and proteinuria appeared to be decreased at the eighth month. In addition, secretion of interleukin-4 and interferon-γ cytokines, immune complexes accumulation/deposition in kidneys, and the renal inflammatory damage were relieved compared to those in mice of model group without B7-2 silencing lentivirus intervention. In conclusion, suppression of B7/CD28 signal by lentivirus-mediated B7-2 gene silencing can reduce the development of experimental lupus nephritis, suggesting it is a potentially useful strategy for decelerating the progression of lupus-like diseases.