Notch 1 signaling regulates peripheral T cell activation
Notch 1 signaling regulates peripheral T cell activation
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DOI：
10.1016/s1074-7613(04)00081-0
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发表时间：
2004-04-01
期刊：
影响因子：
32.4
通讯作者：
Bluestone, JA
中科院分区：
文献类型：
--
作者：
Eagar, TN;Tang, QZ;Bluestone, JA
Notch信号转导已被鉴定为白细胞分化和胸腺成熟的重要调节因子。关于Notch信号在调节成熟T细胞中的作用知之甚少。我们研究了Notch I在体外和体内调节外周T细胞活性的作用。Notch 1与TCR和CD 28的共配导致T细胞活化、增殖和细胞因子产生的显著抑制。这种作用依赖于早老素活性并诱导HES-1的表达，提示Notch 1信号传导。生物化学分析表明Notch I参与后AKT和GSK 3 β磷酸化受到抑制，而其他生物化学信号如TCR和ERK磷酸化保持完整。在体内过继转移模型中观察到类似的效应。因此，Notch 1信号传导可能在调节初始T细胞活化和稳态中起重要作用。
Notch signaling has been identified as an important regulator of leukocyte differentiation and thymic maturation. Less is known about the role of Notch signaling in regulating mature T cells. We examined the role of Notch I in regulating peripheral T cell activity in vitro and in vivo. Coligation of Notch 1 together with TCR and CD28 resulted in a dramatic inhibition of T cell activation, proliferation, and cytokine production. This effect was dependent on presenilin activity and induced the expression of HES-1, suggestive of Notch 1 signaling. Biochemical analysis demonstrated an inhibition of AKT and GSK3beta phosphorylation following Notch I engagement while other biochemical signals such as TCR and ERK phosphorylation remained intact. Similar effects were observed in vivo in an adoptive transfer model. Therefore, Notch 1 signaling may play an important role in regulating naive T cell activation and homeostasis.