自身免疫性T细胞攻击β-细胞导致胰岛素生产缺陷，从而引发I型糖尿病。中国每年有近13000例新发的I型糖尿病患者，长期注射胰岛引起的耐受和糖尿病并发症，严重威胁患者的生命健康。免疫干预自身免疫性T是治疗I型糖尿病的一种理想方式。免疫检查点信号轴PD-1/PD-L1，负调控T细胞的活性，避免活化T细胞对正常组织攻击。本项目拟通过基因编辑巨核细胞表达T细胞负调控配体PD-L1，并在体外大量生产表达PD-L1的血小板。PD-L1血小板及其活化后产生的PD-L1纳米粒可在发炎的胰腺中积累，并抑制胰腺自身反应性T细胞的活性，从而保护β-细胞免受攻击。 通过拯救糖尿病小鼠的β-细胞恢复胰岛素的产生，从而维持患病小鼠的血糖处于正常水平，最终实现对新生I型糖尿病的治疗。相对光谱型T细胞清除单抗药物，PD-L1血小板易于大规模生产，且其毒副作用小，因而具有非常好的临床转化价值和商业应用前景。

Type I diabetes occurs when autoimmune T cells attack beta cells, resulting in defective insulin production.Every year, there are nearly 13,000 newly diagnosed type I diabetes patients in China, whose life and health are seriously threatened by tolerance and diabetes complications caused by long-term injection of pancreatic islets.Immune intervention with autoimmune T is an ideal treatment for type I diabetes.Immune checkpoint signal axis PD-1 / PD-L1 negatively regulates the activity of T cells to avoid the autoimmune attack caused by activated T cells.In this project, megakaryocytes were designed to express t-cell negative regulatory ligand PD-L1 through gene editing, and large quantities of PD-L1 expressing platelets were produced in vitro.PD-L1 platelets and the PD-L1 nanoparticles produced by their activation can accumulate in the inflamed pancreas and inhibit the activity of the pancreas's own reactive T cells, thereby protecting the insulin-producing -beta cells from attack.Treatment for neonatal type I diabetes is achieved by restoring insulin production by saving beta cells in diabetic mice, thereby maintaining normal blood glucose levels in the diseased mice.Compared with monoclonal antibody drugs cleared by T cells of spectral type, PD-L1 platelets are easy to be produced in large scale with small toxic and side effects, so they have very good clinical conversion value and commercial application prospect.