T细胞异常活化致川崎病血管炎的新机制：USF2调控NFAT2信号通路

川崎病（KD）以儿童全身免疫性中小血管炎为特征，是成年后冠心病的独立危险因素。T细胞的异常活化及炎症因子的释放是导致血管炎性损伤的主要机制，目前公认活化T细胞核因子（NFAT）参与T细胞活化环节。我们前期生物信息学预测NFAT2的上游转录因子是上游刺激因子2（USF2），且预实验证实KD病人外周血中USF2的mRNA表达升高，在内皮细胞炎性损伤细胞模型中USF2和NFAT2的变化相关。为此，科学假设：USF2靶向NFAT2是T细胞异常活化导致川崎病血管炎性损伤的机制之一，我们拟系统研究：①KD病人外周血T细胞USF2、NFAT2表达水平与冠脉损害的相关性；②体外实验探讨USF2在T细胞活化中的作用，并验证NFAT2中USF2的结合位点；③KD小鼠模型验证：T细胞中USF2对NFAT2的靶向调控作用，以期为KD的早期干预提供新理论依据和潜在干预靶标。

Kawasaki disease (KD) is characterized by systemic immune vasculitis with small and moderate vessels in children, and is an independent risk factor for coronary heart disease in adulthood. The abnormal activation of T cell and the release of inflammatory factors are the main mechanism leading to vascular inflammatory injury, the nuclear factor of activated T cells (NFAT) are involved in the T cell activation. Bioinformatics analysis indicated that Upstream Transcription Factor2 (USF2) regulated NFAT2 in the upstream link. Our pre-experiments have confirmed the elevated mRNA of USF2 in peripheral blood of patients with KD. There showed the same trend of USF2 and NFAT2 in the inflammatory injury cell model. To this end, we speculated that: USF2 targets to NFAT2 to activate T cell and finally leads to immune vasculitis in KD. We aim to conduct the following researches:①Clarifying the correlation among the expression of USF2, NFAT2 and coronary artery lesions in peripheral blood of patients with KD. ②Clarifying the role of USF2 in T cell activation in vitro cell experiments, and verifying the binding site of USF2 in NFAT2. ③Clarifying the role of USF2 targeting NFAT2 in T cell from KD mouse model. This program may provide a new theoretical basis and potential targets for early prevention and treatment for KD.