Genetic disruption of Nprl depletes regulatory T cells and provokes high levels of proinflammatory cytokines and fibrosis in the kidneys of female mutant mice

摘要

Expression of proinflammatory cytokines and BP was significantly elevated in 1-copy and O-copy mice compared with 2-copy and 4-copy mice. In addition, O-copy and 1-copy mice exhibited drastic reductions in regulatory T cells (Tregs). After rapamycin treatment, Tregs were increased by 17 (P < 0.001) in O-copy mice and 8 (P < 0.001) in 1-copy mice. Renal mRNA and protein levels ol'TLR2 and TLR4 were decreased by 70 in O-copy mice and 50 in 1-copy mice. There were significantly higher levels of Tregs and very low levels of TLR2/TLR4 expression in 4-copy mice (P < 0.001). These findings indicate that the disruption of Nprl in female mice triggers renal immunogenic pathways, which Lransactivate the expression of proinflammatory cytokines and renal fibrosis with elevated BP in mutant animals. The data suggest that rapamycin treatment attenuates proinflammatory cytokine expression, dramatically increases anti-inflammatory cytokines, and substantially reduces BP and renal fibrosis in mutant animals.