Xanthoudakis S, Viola J P, Shaw K T, Luo C, Wallace J D, Bozza P T, Luk D C, Curran T, Rao A
Neurogenetics Program, Department of CNS Research, Hoffmann-LaRoche, Nutley, NJ 07110, USA.
Science. 1996 May 10;272(5263):892-5. doi: 10.1126/science.272.5263.892.
Transcription factors of the NFAT family are thought to play a major role in regulating the expression of cytokine genes and other inducible genes during the immune response. The role of NFAT1 was investigated by targeted disruption of the NFAT1 gene. Unexpectedly, cells from NFAT1 -/- mice showed increased primary responses to Leishmania major and mounted increased secondary responses to ovalbumin in vitro. In an in vivo model of allergic inflammation, the accumulation of eosinophils and levels of serum immunoglobulin E were increased in NFAT1 -/- mice. These results suggest that NFAT1 exerts a negative regulatory influence on the immune response.
NFAT家族的转录因子被认为在免疫反应过程中对细胞因子基因和其他诱导基因的表达调控起主要作用。通过对NFAT1基因进行靶向破坏来研究NFAT1的作用。出乎意料的是,来自NFAT1 -/-小鼠的细胞在体外对利什曼原虫主要种的初次反应增强,对卵清蛋白的二次反应也增强。在过敏性炎症的体内模型中,NFAT1 -/-小鼠的嗜酸性粒细胞积累和血清免疫球蛋白E水平升高。这些结果表明NFAT1对免疫反应发挥负调节作用。