The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling cascade is an evolutionarily conserved signal transduction pathway that regulates many vital cellular processes, including immune function and hematopoiesis. Human genetic variants that disrupt JAK-STAT signaling are being found to cause a rapidly increasing number of diseases, including both germline-encoded inborn errors of immunity (IEI) and acquired somatic variants, causing a so-called phenocopy of the IEI. Multiple genetic mechanisms are responsible for this growing group of JAK-STAT diseases including loss-of-function, gain-of-function, and dominant negative effects. In this review, we discuss the clinical presentation and pathogenesis of all currently described JAK-STAT defects, as well as provide an overview of the guiding principles to consider in diagnosing and treating these conditions.

中文翻译：

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JAK-STAT 信号通路、免疫缺陷、炎症、免疫失调和先天性免疫缺陷。


Janus 激酶信号转导和转录激活因子 （JAK-STAT） 信号级联反应是一种进化上保守的信号转导通路，可调节许多重要的细胞过程，包括免疫功能和造血功能。研究发现，破坏 JAK-STAT 信号传导的人类遗传变异会导致数量迅速增加的疾病，包括种系编码的先天免疫缺陷 （IEI） 和获得性体细胞变异，从而导致所谓的 IEI 表型复制。多种遗传机制导致了这一不断增长的 JAK-STAT 疾病组，包括功能丧失、功能获得和显性负面影响。在本综述中，我们讨论了目前描述的所有 JAK-STAT 缺陷的临床表现和发病机制，并概述了诊断和治疗这些疾病时需要考虑的指导原则。