Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas 75708, USA.
Nat Commun. 2016 Dec 16;7:13896. doi: 10.1038/ncomms13896.
Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1 cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1 cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1 cells in islet allograft-transplanted mice is involved in the production of IL-22 and in the reduced inflammatory response to allografts. Vaccination of T1D mice with a CpG oligonucleotide TLR9 agonist (ODN 1585) enhances expansion of IL-22-producing CD3-NK1.1 cells in the liver and prolongs allograft survival. Our study identifies a role for liver NK1.1 cells, IL-22 and CpG oligonucleotides in the induction of tolerance to islet allografts in the liver parenchyma.
胰岛移植是治疗 1 型糖尿病（T1D）的一种很有前途的潜在方法。胰岛同种异体移植物可以在肝实质中长期存活。在这里，我们发现肝 NK1.1 细胞在 T1D 小鼠模型中诱导同种异体移植物耐受。NK1.1 细胞的耐受性是通过产生 IL-22 介导的，它可以延长移植物的存活并增加胰岛素的分泌。肝 NK1.1 细胞在胰岛同种异体移植小鼠中表达增加的 NKG2A 参与了 IL-22 的产生，并减轻了同种异体移植物的炎症反应。用 CpG 寡核苷酸 TLR9 激动剂（ODN 1585）对 T1D 小鼠进行疫苗接种可增强肝脏中产生 IL-22 的 CD3-NK1.1 细胞的扩增，并延长同种异体移植物的存活时间。我们的研究确定了肝 NK1.1 细胞、IL-22 和 CpG 寡核苷酸在诱导肝实质中胰岛同种异体移植物耐受中的作用。
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