State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan 610041, China.
Nano Lett. 2021 May 26;21(10):4437-4446. doi: 10.1021/acs.nanolett.1c01131. Epub 2021 May 6.
A failure in immune tolerance leads to autoimmune destruction of insulin-producing β-cells, leading to type 1 diabetes (T1D). Inhibiting autoreactive T cells and inducing regulatory T cells (Tregs) to re-establish immune tolerance are promising approaches to prevent the onset of T1D. Here, we investigated the ability of tetrahedral framework nucleic acids (tFNAs) to induce immune tolerance and prevent T1D in nonobese diabetic (NOD) mice. In prediabetic NOD mice, tFNAs treatment led to maintenance of normoglycemia and reduced incidence of diabetes. Moreover, the tFNAs (250 nM) treatment preserved the mass and function of β-cells, increased the frequency of Tregs, and suppressed autoreactive T cells, leading to immune tolerance. Collectively, our results demonstrate that tFNAs treatment aids glycemic control, provides β-cell protection, and prevents the onset of T1D in NOD mice by immunomodulation. These results highlight the potential of tFNAs for the prevention of autoimmune T1D.
免疫耐受失败导致胰岛素产生β细胞的自身免疫破坏，从而引发 1 型糖尿病（T1D）。抑制自身反应性 T 细胞并诱导调节性 T 细胞（Tregs）重建免疫耐受是预防 T1D 发病的有前途的方法。在这里，我们研究了四面体型核酸（tFNAs）诱导免疫耐受和预防非肥胖型糖尿病（NOD）小鼠 T1D 的能力。在糖尿病前期 NOD 小鼠中，tFNAs 治疗可维持正常血糖水平并降低糖尿病的发病率。此外，tFNAs（250 nM）治疗可维持β细胞的质量和功能，增加 Tregs 的频率，并抑制自身反应性 T 细胞，从而诱导免疫耐受。总之，我们的结果表明，tFNAs 治疗通过免疫调节有助于控制血糖、提供β细胞保护并预防 NOD 小鼠 T1D 的发生。这些结果突出了 tFNAs 在预防自身免疫性 T1D 中的潜力。
