Dipartimento di Medicina Interna, Università Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy.
Expert Opin Ther Targets. 2011 Jun;15(6):695-702. doi: 10.1517/14728222.2011.561319. Epub 2011 Mar 11.
IL-21, a new member of the type 1 cytokine superfamily, is produced by various subsets of CD4(+) T cells and binds to a composite receptor that consists of a specific receptor, termed IL-21 receptor and the common γ-chain subunit. Initially considered to be a critical regulator of T and B cell function, IL-21 is now known to regulate the activity of many other cell types, including both immune and non-immune cells.
In this review, we discuss the biological features of IL-21 and summarize recent advances in the pathogenic role of IL-21 in chronic inflammatory diseases. Moreover, we discuss why IL-21 blockers can have a place in the therapeutic armamentarium for patients with immune-mediated diseases and the potential risks of such treatments.
Data emerging from studies in human and experimental models of autoimmunity suggest that IL-21 is critically involved in the initiation and/or progression of inflammatory reactions where self-reactive immune cells or antibodies cause damage in tissue. Thus, theoretically, targeting IL-21 could help attenuate the activation of inflammatory pathways and facilitate the resolution of tissue damaging immune responses. However, one should also take into consideration some potential risks that could derive from the blockade of IL-21.
白细胞介素 21(IL-21)是 I 型细胞因子超家族的新成员,由各种 CD4(+) T 细胞亚群产生,并与由特定受体(称为白细胞介素 21 受体)和共同 γ 链亚基组成的复合受体结合。最初被认为是 T 细胞和 B 细胞功能的关键调节剂,现在已知白细胞介素 21 可调节许多其他细胞类型的活性,包括免疫细胞和非免疫细胞。
在这篇综述中,我们讨论了白细胞介素 21 的生物学特征,并总结了白细胞介素 21 在慢性炎症性疾病中的致病作用的最新进展。此外,我们还讨论了为什么白细胞介素 21 阻断剂可以成为免疫介导性疾病患者治疗武器库中的一部分,以及这种治疗的潜在风险。
来自自身免疫性疾病的人类和实验模型研究的数据表明,白细胞介素 21 是炎症反应的启动和/或进展的关键因素,其中自身反应性免疫细胞或抗体在组织中造成损伤。因此,从理论上讲,靶向白细胞介素 21 可以帮助减弱炎症途径的激活,并促进组织损伤免疫反应的解决。然而,还应该考虑到阻断白细胞介素 21 可能带来的一些潜在风险。