Nagy Zsuzsanna S, Ross Jeremy, Cheng Hanyin, Stepkowski Stanislaw M, Kirken Robert A
University of Texas Health Science Center at Houston, Department of Integrative Biology and Pharmacology, 77030, USA.
Crit Rev Immunol. 2004;24(2):87-110. doi: 10.1615/critrevimmunol.v24.i2.10.
Regulation of T- and B-lymphocyte survival and death is crucial for maintaining immune homeostasis. Unresponsiveness to death signals can result in lymphoproliferative disorders including cancer and autoimmunity, whereas lymphocytes hypersensitive to such signals can be manifested as immunodeficiencies. Often within these cells, cytokines and their receptors regulate the critical balance between life and death. It is becoming ever more apparent that within these effector cascades, Janus tyrosine kinases (Jak) and signal transducers and activators of transcription (Stat) act as key regulatory components. Invaluable knowledge about Jaks and Stats has arisen from mice made genetically deficient in these mqlecules, tumor models, and proteomics/genomics, which has begun to define their role in survival versus apoptosis. These findings have also suggested how Jaks and Stats might be manipulated for therapeutic intervention in lymphoid-derived diseases. This review seeks to focus on the role of Jak tyrosine kinases and Stat transcription factors in mediating the lymphocyte life cycle.
T 淋巴细胞和 B 淋巴细胞存活与死亡的调节对于维持免疫稳态至关重要。对死亡信号无反应可导致包括癌症和自身免疫在内的淋巴细胞增殖性疾病,而对这类信号高度敏感的淋巴细胞则可表现为免疫缺陷。通常在这些细胞内,细胞因子及其受体调节生死之间的关键平衡。越来越明显的是,在这些效应级联反应中,Janus 酪氨酸激酶(Jak)和信号转导及转录激活因子(Stat)作为关键调节成分发挥作用。通过对这些分子基因缺失的小鼠、肿瘤模型以及蛋白质组学/基因组学的研究,已经获得了关于 Jak 和 Stat 的宝贵知识,这开始明确它们在存活与凋亡中的作用。这些发现还提示了如何操纵 Jak 和 Stat 以对淋巴源性疾病进行治疗干预。本综述旨在聚焦 Jak 酪氨酸激酶和 Stat 转录因子在介导淋巴细胞生命周期中的作用。