Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Clinical Immunology Center, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Trends Mol Med. 2022 Jul;28(7):596-612. doi: 10.1016/j.molmed.2022.04.010. Epub 2022 May 24.
Autoimmune diseases are characterized by dysregulation and aberrant activation of cells in the immune system. Therefore, restoration of the immune balance represents a promising therapeutic target in autoimmune diseases. Interleukin-2 (IL-2) can promote the expansion and differentiation of different immune cell subsets dose-dependently. At high doses, IL-2 can promote the differentiation and expansion of effector and memory T cells, whereas at low doses, IL-2 can promote the differentiation, survival, and function of regulatory T (T) cells, a CD4 T cell subset that is essential for the maintenance of immune homeostasis and immune tolerance. Therefore, IL-2 exerts immunostimulatory and immunosuppressive effects in autoimmune diseases. The immunoregulatory role of low-dose IL-2 has sparked excitement for the therapeutic exploration of modulating the IL-2-T axis in the context of autoimmune diseases. In this review, we discuss recent advances in the therapeutic potential of IL-2 or IL-2-derived molecules in the treatment of autoimmune diseases.
自身免疫性疾病的特征是免疫系统中的细胞失调和异常激活。因此,恢复免疫平衡是自身免疫性疾病的一个有前途的治疗靶点。白细胞介素-2(IL-2)可以剂量依赖性地促进不同免疫细胞亚群的扩增和分化。高剂量的 IL-2 可以促进效应和记忆 T 细胞的分化和扩增,而低剂量的 IL-2 可以促进调节性 T(T)细胞的分化、存活和功能,调节性 T 细胞是维持免疫稳态和免疫耐受所必需的 CD4 T 细胞亚群。因此,IL-2 在自身免疫性疾病中发挥免疫刺激和免疫抑制作用。低剂量 IL-2 的免疫调节作用激发了人们对调节自身免疫性疾病中 IL-2-T 轴的治疗探索的兴趣。在这篇综述中,我们讨论了 IL-2 或 IL-2 衍生分子在治疗自身免疫性疾病方面的治疗潜力的最新进展。