Low-Dose IL-2 Therapy in Transplantation, Autoimmunity, and Inflammatory Diseases
Low-Dose IL-2 Therapy in Transplantation, Autoimmunity, and Inflammatory Diseases
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DOI：
10.4049/jimmunol.1900733
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发表时间：
2019-12-01
影响因子：
4.4
通讯作者：
Dana, Reza
中科院分区：
文献类型：
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作者：
Tahvildari, Maryam;Dana, Reza
调节性T细胞（Regulatory T cells，Tcells）在诱导和维持免疫稳态和自身耐受中起着重要作用。T细胞持续表达IL-2的高亲和力受体。IL-2是一种多效性细胞因子，是THP的关键存活因子。它通过促进Foxp 3的表达和随后的免疫调节细胞因子的产生来维持THBE的抑制功能。在实验模型中，低剂量IL-2的给药被证明是预防同种异体移植物排斥和治疗自身免疫和炎症状况的有希望的方法。IL-2与其mAb（JES 6 -1）的组合也已显示增加IL-2的t（1/2）并进一步增强Treg频率和功能。低剂量IL-2疗法已在几项临床试验中用于治疗诸如丙型肝炎血管炎、移植物抗宿主病、1型糖尿病和系统性红斑狼疮等病症。在本文中，我们总结了我们的研究结果低剂量IL-2治疗角膜移植和审查最近的研究，重点是使用低剂量IL-2在移植，自身免疫，和其他炎症条件。我们还讨论了进一步研究的潜在领域，旨在优化目前的低剂量IL-2方案。
Regulatory T cells (Tregs) play a central role in the induction and maintenance of immune homeostasis and self-tolerance. Tregs constantly express the high-affinity receptor to IL-2. IL-2 is a pleiotropic cytokine and a key survival factor for Tregs. It maintains Tregs' suppressive function by promoting Foxp3 expression and subsequent production of immunoregulatory cytokines. Administration of low-dose IL-2 is shown to be a promising approach to prevent allograft rejection and to treat autoimmune and inflammatory conditions in experimental models. The combination of IL-2 with its mAb (JES6-1) has also been shown to increase the t(1/2) of IL-2 and further enhance Treg frequencies and function. Low-dose IL-2 therapy has been used in several clinical trials to treat conditions such as hepatitis C vasculitis, graft-versus-host disease, type 1 diabetes, and systemic lupus erythematosus. In this paper, we summarize our findings on low-dose IL-2 treatment in corneal allografting and review recent studies focusing on the use of low-dose IL-2 in transplantation, autoimmunity, and other inflammatory conditions. We also discuss potential areas of further investigation with the aim to optimize current low-dose IL-2 regimens.