1 型糖尿病中 CD4 T 细胞的单细胞分析：从鼠到人，如何进行机制研究。
Single-Cell Analysis of CD4 T Cells in Type 1 Diabetes: From Mouse to Man, How to Perform Mechanistic Studies.
机构信息
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA.
Division of Endocrinology and Metabolism, University of California, San Diego, San Diego, CA.
出版信息
Diabetes. 2019 Oct;68(10):1886-1891. doi: 10.2337/dbi18-0064.
Type 1 diabetes is the prototypical CD4 T cell-mediated autoimmune disease. Its genetic linkage to a single polymorphism at position 57 of the HLA class II DQβ chain makes it unique to study the molecular link between HLA and disease. However, investigating this relationship has been limited by a series of anatomical barriers, the small size and dispersion of the insulin-producing organ, and the scarcity of appropriate techniques and reagents to interrogate antigen-specific CD4 T cells both in man and rodent models. Over the past few years, single-cell technologies, paired with new biostatistical methods, have changed this landscape. Using these tools, we have identified the first molecular link between MHC class II and the onset of type 1 diabetes. The translation of these observations to man is within reach using similar approaches and the lessons learned from rodent models.
1 型糖尿病是典型的 CD4 T 细胞介导的自身免疫性疾病。其与 HLA 类 II DQβ 链第 57 位单一位点多态性的遗传关联使其成为研究 HLA 与疾病之间分子联系的独特模型。然而，对这种关系的研究受到一系列解剖学障碍的限制，即产生胰岛素的器官体积小且分散，以及缺乏适当的技术和试剂来检测人和啮齿动物模型中抗原特异性 CD4 T 细胞。在过去的几年中，单细胞技术与新的生物统计学方法相结合，改变了这种局面。使用这些工具，我们已经确定了 MHC 类 II 与 1 型糖尿病发病之间的第一个分子联系。使用类似的方法和从啮齿动物模型中吸取的经验教训，这些观察结果在人类中的转化是可行的。
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