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低剂量 IL-2 治疗自身免疫病的新兴机制和应用。

Emerging mechanisms and applications of low-dose IL-2 therapy in autoimmunity.

机构信息

Department of Laboratory Medicine, Affiliated Hospital of Jiangnan University, Wuxi, China; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.

出版信息

Cytokine Growth Factor Rev. 2022 Oct;67:80-88. doi: 10.1016/j.cytogfr.2022.06.003. Epub 2022 Jun 30.

Abstract

Interleukin 2 (IL-2) is a pleiotropic cytokine that elicits both immunogenic and tolerogenic immune response essential for homeostasis. Initial clinical application of IL-2 based therapy was hampered by its function on broad spectrum of cells expressing corresponding receptors, which exerts uncontrolled side effects in clinical trials. While recent progress on structural modification or adjusted regimen of IL-2, revolutionized the use of IL-2 in immunomodulation process that requires stringent selection of effector cells, such as promotion of T cells for tolerance or invigoration of CD8 T cells against infection and cancer. Low-dose IL-2 therapy is amongst these succuss and is proved to be a promising immunotherapy to treat a broad range of autoimmune and inflammatory diseases. This article will review major recent advances in fundamental research on IL-2 as well as significant progress made in clinical trials where patients received low-dose IL-2 therapy. This knowledge also helps design further optimized IL-2 therapies for a broader application in treating human disease.

摘要

白细胞介素 2(IL-2)是一种多效细胞因子,可引发免疫原性和耐受性免疫反应,这对维持体内平衡至关重要。最初基于白细胞介素 2 的治疗方法的临床应用受到其对表达相应受体的广谱细胞的功能的阻碍,这在临床试验中产生了不受控制的副作用。尽管最近在白细胞介素 2 的结构修饰或调整方案方面取得了进展,但其在免疫调节过程中的使用发生了革命性变化,这需要严格选择效应细胞,例如促进 T 细胞耐受或增强 CD8 T 细胞对抗感染和癌症。低剂量白细胞介素 2 治疗就是其中的成功案例,并已被证明是一种有前途的免疫疗法,可治疗广泛的自身免疫性和炎症性疾病。本文将综述白细胞介素 2 基础研究方面的主要最新进展以及临床试验方面的重大进展,患者接受了低剂量白细胞介素 2 治疗。这些知识还有助于设计进一步优化的白细胞介素 2 疗法,以更广泛地应用于治疗人类疾病。

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