Natural Protection From Type 1 Diabetes in NOD Mice Is Characterized by a Unique Pancreatic Islet Phenotype
Natural Protection From Type 1 Diabetes in NOD Mice Is Characterized by a Unique Pancreatic Islet Phenotype
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DOI：
10.2337/db20-0945
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发表时间：
2021-04-01
期刊：
影响因子：
7.7
通讯作者：
Wong, F. Susan
中科院分区：
文献类型：
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作者：
Boldison, Joanne;Thayer, Terri C.;Wong, F. Susan
NOD小鼠发生自发性1型糖尿病，具有与人类疾病非常相似的疾病特征。然而，一部分NOD小鼠自然地受到保护，不会发生糖尿病，目前，表征这一队列的研究非常有限。在这里，使用免疫荧光和多参数流式细胞术，我们专注于胰岛形态和免疫浸润自然保护NOD小鼠中观察到的。我们表明，自然保护的NOD小鼠的特点是含胰岛素的，较小的，胰岛的频率增加。尽管小鼠保持无糖尿病，但仍存在丰富的免疫浸润。然而，这种免疫浸润倾向于T细胞和B细胞区室中的调节表型。胰岛中产生IL-10的B细胞和相关细胞表面标志物的频率增加。常驻记忆CD 69（+）CD 8（+）T细胞显示出向CD 103表达减少的显著转变，而CD 4（+）T细胞具有FoxP 3（+）CTLA 4（+）表达增加。这些数据表明，自然保护的NOD小鼠具有独特的胰岛特征，并提供了对胰岛内调节机制的新见解。
The NOD mouse develops spontaneous type 1 diabetes, with some features of disease that are very similar to the human disease. However, a proportion of NOD mice are naturally protected from developing diabetes, and currently, studies characterizing this cohort are very limited. Here, using both immunofluorescence and multiparameter flow cytometry, we focus on the pancreatic islet morphology and immune infiltrate observed in naturally protected NOD mice. We show that naturally protected NOD mice are characterized by an increased frequency of insulin-containing, smaller-sized, pancreatic islets. Although mice remain diabetes free, florid immune infiltrate remains. However, this immune infiltrate is skewed toward a regulatory phenotype in both T- and B-cell compartments. Pancreatic islets have an increased frequency of IL-10-producing B cells and associated cell surface markers. Resident memory CD69(+)CD8(+) T cells show a significant shift toward reduced CD103 expression, while CD4(+) T cells have increased FoxP3(+)CTLA4(+) expression. These data indicate that naturally protected NOD mice have a unique islet signature and provide new insight into regulatory mechanisms within pancreatic islets.