Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Sci Signal. 2010 Aug 17;3(135):re5. doi: 10.1126/scisignal.3135re5.
The thymus serves as the primary site for the lifelong formation of new T lymphocytes; hence, it is essential for the maintenance of an effective immune system. Although thymocyte development has been widely studied, the mechanisms involved are incompletely defined. A comprehensive understanding of the molecular events that control regular thymocyte development will not only shed light on the physiological control of T cell differentiation but also probably provide insight into the pathophysiology of T cell immunodeficiencies, the molecular basis that underpins autoimmunity, and the mechanisms that instigate the formation of T cell lymphomas. Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in thymocyte development, although not all of their downstream mediators have yet been identified. Here, we discuss experimental evidence that argues for a critical role of the PI3K-phosphoinositide-dependent protein kinase (PDK1)-protein kinase B (PKB) signaling pathway in the development of both normal and malignant thymocytes, and we highlight molecules that can potentially be targeted therapeutically.
胸腺是新 T 淋巴细胞终身形成的主要场所；因此，它对于维持有效的免疫系统至关重要。尽管胸腺细胞的发育已经得到了广泛的研究，但其中涉及的机制尚未完全确定。全面了解控制正常胸腺细胞发育的分子事件不仅将揭示 T 细胞分化的生理控制机制，而且可能为 T 细胞免疫缺陷、自身免疫的分子基础以及引发 T 细胞淋巴瘤形成的机制提供深入了解。磷脂酰肌醇 3-激酶 (PI3Ks) 在胸腺细胞发育中发挥着关键作用，尽管尚未确定其所有下游介质。在这里，我们讨论了支持 PI3K-磷酸肌醇依赖性蛋白激酶 (PDK1)-蛋白激酶 B (PKB) 信号通路在正常和恶性胸腺细胞发育中关键作用的实验证据，并强调了可能具有治疗潜力的分子。
