Cytokines function as communication tools of the immune system, serving critical functions in many biological responses and shaping the immune response. When cytokine production or their biological activity goes awry, the homeostatic balance of the immune response is altered, leading to the development of several pathologies such as autoimmune and inflammatory disorders. Cytokines bind to specific receptors on cells, triggering the activation of intracellular enzymes known as Janus kinases (JAKs). The JAK family comprises four members, JAK1, JAK2, JAK3 and tyrosine kinase 2, which are critical for intracellular cytokine signalling. Since the mid-2010s multiple JAK inhibitors have been approved for inflammatory and haematological indications. Currently, approved JAK inhibitors have demonstrated clinical efficacy; however, improved selectivity for specific JAKs is likely to enhance safety profiles, and different strategies have been used to accomplish enhanced JAK selectivity. In this update, we discuss the background of JAK inhibitors, current approved indications and adverse effects, along with new developments in this field. We address the issue of JAK selectivity and its relevance in terms of efficacy, and describe new modalities of JAK targeting, as well as new aspects of JAK inhibitor action.

细胞因子作为免疫系统的通讯工具，在许多生物反应中发挥关键作用并塑造免疫反应。当细胞因子的产生或其生物活性出现问题时，免疫反应的稳态平衡就会改变，导致多种病理学的发展，例如自身免疫性疾病和炎症性疾病。细胞因子与细胞上的特定受体结合，触发称为 Janus 激酶 (JAK) 的细胞内酶的激活。 JAK 家族包括四个成员：JAK1、JAK2、JAK3 和酪氨酸激酶 2，它们对于细胞内细胞因子信号传导至关重要。自 2010 年代中期以来，多种 JAK 抑制剂已被批准用于炎症和血液学适应症。目前，已批准的JAK抑制剂已显示出临床疗效；然而，提高特定 JAK 的选择性可能会增强安全性，并且已使用不同的策略来实现增强的 JAK 选择性。在本次更新中，我们讨论了 JAK 抑制剂的背景、当前批准的适应症和不良反应，以及该领域的新进展。我们解决了 JAK 选择性问题及其在功效方面的相关性，并描述了 JAK 靶向的新模式以及 JAK 抑制剂作用的新方面。