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Abstract：
The JAK-STAT pathway is a crucial cellular signaling cascade, including an intricate network of Protein-protein interactions (PPIs) responsible for its regulation. It mediates the activities of several cytokines, interferons, and growth factors and transduces extracellular signals into transcriptional programs to regulate cell growth and differentiation. It is essential for the development and function of both innate and adaptive immunities, and its aberrant deregulation was highlighted in neuroinflammatory diseases and in crucial mechanisms for tumor cell recognition and tumor-induced immune escape. For its involvement in a multitude of biological processes, it can be considered a valuable target for the development of drugs even if a specific focus on possible side effects associated with its inhibition is required. Herein, we review the possibilities to target JAK-STAT by focusing on its natural inhibitors as the suppressor of cytokine signaling (SOCS) proteins. This protein family is a crucial checkpoint inhibitor in immune homeostasis and a valuable target in immunotherapeutic approaches to cancer and immune deficiency disorders.
摘要：
JAK-STAT通路是一个重要的细胞信号级联,包括负责其调节的蛋白质-蛋白质相互作用（PPI）的复杂网络。它介导几种细胞因子的活性，干扰素,和生长因子，并将细胞外信号转换为转录程序以调节细胞生长和分化。它对先天免疫和适应性免疫的发育和功能至关重要，它的异常失调在神经炎症性疾病以及肿瘤细胞识别和肿瘤诱导的免疫逃逸的关键机制中得到了强调。因为它参与了许多生物过程，它可以被认为是药物开发的有价值的目标，即使需要对与其抑制相关的可能副作用有特别的关注。在这里，我们通过关注JAK-STAT的天然抑制剂作为细胞因子信号传导（SOCS）蛋白的抑制剂，回顾了靶向JAK-STAT的可能性。该蛋白质家族是免疫稳态中的关键检查点抑制剂，也是癌症和免疫缺陷性疾病的免疫治疗方法中的有价值的靶标。
