Kolios Antonios G A, Tsokos George C, Klatzmann David
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Nat Rev Rheumatol. 2021 Dec;17(12):749-766. doi: 10.1038/s41584-021-00707-x. Epub 2021 Nov 2.
Failure of regulatory T (T) cells to properly control immune responses leads invariably to autoimmunity and organ damage. Decreased numbers or impaired function of T cells, especially in the context of inflammation, has been documented in many human autoimmune diseases. Restoration of T cell fitness and/or expansion of their numbers using low-dose natural IL-2, the main cytokine driving T cell survival and function, has demonstrated clinical efficacy in early clinical trials. Genetically modified IL-2 with an extended half-life and increased selectivity for T cells is now in clinical development. Administration of IL-2 combined with therapies targeting other pathways involved in the expression of autoimmune diseases should further enhance its therapeutic potential. Ongoing clinical efforts that capitalize on the early clinical success of IL-2 treatment should bring the use of this cytokine to the forefront of biological treatments for autoimmune diseases.
调节性T（Treg）细胞无法有效控制免疫反应，必然会导致自身免疫和器官损伤。在许多人类自身免疫性疾病中，已证实Treg细胞数量减少或功能受损，尤其是在炎症背景下。使用低剂量天然白细胞介素-2（IL-2）恢复Treg细胞的健康状态和/或增加其数量，IL-2是驱动Treg细胞存活和功能的主要细胞因子，在早期临床试验中已显示出临床疗效。具有延长半衰期和对Treg细胞更高选择性的基因工程IL-2目前正在进行临床开发。将IL-2与针对自身免疫性疾病表达所涉及的其他途径的疗法联合使用，应能进一步提高其治疗潜力。利用IL-2治疗早期临床成功的正在进行的临床研究，应能使这种细胞因子的应用成为自身免疫性疾病生物治疗的前沿。
