Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, 1359 TAMU, 8447 Riverside Pkwy, MREB 2, Bryan, TX, 77807-3260, USA.
Curr Diab Rep. 2019 Aug 30;19(10):89. doi: 10.1007/s11892-019-1213-7.
Type 1 diabetes (T1D) is an autoimmune disease in which the immune cells selectively destroy the pancreatic beta (β) cells and results in the deficiency of insulin production. The optimal treatment strategy for T1D should be preventing of β-cell destruction in the pancreas. The purpose of this review is to discuss the immunological therapeutic mechanisms that will help to understand the development and control of β-cell destruction. The review also presents a novel method for development of autoantigen (Ag)-specific regulatory T cells (Tregs) for T1D immunotherapy.
Pancreatic-resident Tregs have the ability to dramatically suppress hyperactive immune cells. Islet cell transplantation is another attractive approach to replace the failed β cells. Due to the limited source of islet cells, research is going on in the use of animal cells and adult stem cells that may be derived from the patient's own body to produce β cells for transplantation. The mechanism behind the pancreatic β-cell destruction is largely unknown. In this review, a novel approach for the generation of tissue-associated Tregs from stem cells is considered. The stem cell-derived tissue-associated Tregs have the ability to home to the damaged pancreas to prevent the destruction. The review also provides new insights on the mechanism on how these suppressive immune cells protect the pancreas from the destruction of autoimmune cells. A novel method to develop functional auto Ag-specific Tregs that are derived from induced pluripotent stem cells (iPSCs), i.e., iPSC-Tregs, is discussed. Adoptive transfer of the iPSC-Tregs can substantially suppress T1D development in a murine model.
1 型糖尿病（T1D）是一种自身免疫性疾病，其中免疫细胞选择性地破坏胰岛β（β）细胞，导致胰岛素产生不足。T1D 的最佳治疗策略应该是防止胰腺中β细胞的破坏。本综述的目的是讨论有助于理解β细胞破坏的发展和控制的免疫治疗机制。该综述还介绍了一种用于开发自身抗原（Ag）特异性调节性 T 细胞（Tregs）用于 T1D 免疫治疗的新方法。
驻留于胰腺的 Tregs 具有显著抑制过度活跃免疫细胞的能力。胰岛细胞移植是另一种有吸引力的方法来替代功能失调的β细胞。由于胰岛细胞来源有限，研究正在进行中，使用动物细胞和成人干细胞，这些细胞可能来自患者自身，以产生用于移植的β细胞。胰岛β细胞破坏的机制在很大程度上尚不清楚。在本综述中，考虑了一种从干细胞产生组织相关 Tregs 的新方法。干细胞衍生的组织相关 Tregs 具有归巢到受损胰腺以防止破坏的能力。该综述还提供了关于这些抑制性免疫细胞如何保护胰腺免受自身免疫细胞破坏的机制的新见解。讨论了一种从诱导多能干细胞（iPSCs），即 iPSC-Tregs 中开发功能性自身 Ag 特异性 Tregs 的新方法。iPSC-Tregs 的过继转移可以显著抑制小鼠模型中的 T1D 发展。
