Janus 激酶信号转导和转录激活因子 (JAK-STAT) 通路是从细胞外环境到细胞核信号转导的范例。它在造血、免疫平衡、组织稳态和肿瘤监测等生理功能中发挥着关键作用。该途径的失调可能导致各种疾病，例如免疫缺陷、自身免疫性疾病、血液系统疾病和癌症。由于其在维持人类健康和参与疾病方面的关键作用，人们对该途径进行了广泛的研究，从基础研究到医学应用。该通路结构生物学的进展使我们能够深入了解信号级联如何在分子水平上发挥作用，为针对该通路的治疗开发奠定了基础。人们已经开发出多种策略来恢复其正常功能，具有广阔的治疗潜力。对这些分子机制的加深理解，再加上蛋白质工程方法的进步，使我们能够为靶向治疗应用设计具有定制特性的细胞因子，从而提高其效率和安全性。在这篇综述中，我们概述了控制该通路关键节点的结构基础，提供了信号转导过程的全面概述。此外，我们探索了细胞因子工程的最新进展，以促进该途径的治疗开发。© 2024。作者。

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway serves as a paradigm for signal transduction from the extracellular environment to the nucleus. It plays a pivotal role in physiological functions, such as hematopoiesis, immune balance, tissue homeostasis, and surveillance against tumors. Dysregulation of this pathway may lead to various disease conditions such as immune deficiencies, autoimmune diseases, hematologic disorders, and cancer. Due to its critical role in maintaining human health and involvement in disease, extensive studies have been conducted on this pathway, ranging from basic research to medical applications. Advances in the structural biology of this pathway have enabled us to gain insights into how the signaling cascade operates at the molecular level, laying the groundwork for therapeutic development targeting this pathway. Various strategies have been developed to restore its normal function, with promising therapeutic potential. Enhanced comprehension of these molecular mechanisms, combined with advances in protein engineering methodologies, has allowed us to engineer cytokines with tailored properties for targeted therapeutic applications, thereby enhancing their efficiency and safety. In this review, we outline the structural basis that governs key nodes in this pathway, offering a comprehensive overview of the signal transduction process. Furthermore, we explore recent advances in cytokine engineering for therapeutic development in this pathway.© 2024. The Author(s).