对促甲状腺素受体（TSHR）免疫耐受缺失是Graves病（GD）的重要免疫机制，重建对其耐受将可能成为预防GD的有效方法。本研究前期通过在新生期肌肉注射载体表达TSHR基因或蛋白成功诱导了免疫耐受、预防了实验性GD的发生。既往研究采用的主要是病毒表达载体，病毒载体难以在人体使用。本课题将全部采用TSHR蛋白诱导免疫耐受，通过新生期不同时间及不同剂量诱导确定最佳诱导时机及最佳剂量，为下一步人体应用提供可靠实验依据。通过免疫组库测序及单细胞测序等技术探索预测新生耐受诱导成功的生物学标志物。该研究是利用蛋白疫苗预防人类自身免疫性疾病的重要临床前研究，具有重要的科学价值和临床应用前景。

Loss of the immune tolerance to thyroid stimulating hormone receptor (TSHR) being the important immunologic mechanism of Graves’ disease (GD), the reconstruction of its tolerance would be an effective method to prevent GD. In the previous research，immune tolerance was induced successfully by intramuscular injection with TSHR gene expressed in vector or TSHR protein in neonatal animals, then experimental GD could be prevented in the adults. Early studies mainly used viral expressed vector, which is difficult to apply in humans. The project will all use TSHR protein to induce immune tolerance by different time in neonates and different dosage to confirm the optimal time and dosage of induction, then provide a reliable experimental evidence for its next application of human in future. Additionally, biomarkers for predicting the successful induction of neonatal tolerance were explored by the technologies of immune repertoire sequencing and single-cell sequencing. The project, as an important pre-clinical research using protein vaccine to prevent autoimmune diseases on humans, will be of important scientific value and clinical applied prospect.