Section for Immunobiology, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Eur J Immunol. 2018 Jul;48(7):1211-1216. doi: 10.1002/eji.201847498. Epub 2018 Apr 25.
Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic beta cells and is partly caused by deficiencies in the Foxp3 regulatory T-cell (Treg) compartment. Conversely, therapies that increase Treg function can prevent autoimmune diabetes in animal models. The majority of Tregs develop in the thymus (tTregs), but a proportion of Foxp3 Tregs is generated in the periphery (pTregs) from Foxp3 CD4 T-cell precursors. Whether pTregs play a distinct role in T1D has not yet been explored. We report here that pTregs are a key modifier of disease in the nonobese diabetic (NOD) mouse model for T1D. We generated NOD mice deficient for the Foxp3 enhancer CNS1 involved in pTreg induction. We show that CNS1 knockout decreased the frequency of pTregs and increased the risk of diabetes. Our results show that pTregs fulfill an important non-redundant function in the prevention of beta cell autoimmunity that causes T1D.
1 型糖尿病（T1D）是由胰腺β细胞的自身免疫破坏引起的，部分原因是 Foxp3 调节性 T 细胞（Treg）区室的缺陷。相反，增加 Treg 功能的疗法可以预防动物模型中的自身免疫性糖尿病。大多数 Tregs 在胸腺（tTregs）中发育，但一部分 Foxp3 Tregs 是从 Foxp3 CD4 T 细胞前体在外周（pTregs）中产生的。pTregs 是否在 T1D 中发挥独特作用尚未得到探索。我们在这里报告称，pTregs 是 T1D 的非肥胖型糖尿病（NOD）小鼠模型中疾病的关键修饰因子。我们生成了缺乏 Foxp3 增强子 CNS1 的 NOD 小鼠，该增强子参与 pTreg 的诱导。我们表明 CNS1 敲除降低了 pTreg 的频率，并增加了糖尿病的风险。我们的结果表明，pTregs 在预防导致 T1D 的β细胞自身免疫中发挥了重要的非冗余功能。
