Natural killer cell migration in pregnancy and immunosurveillance regulated by PI3K

一类专门感知癌细胞并摧毁它们的白细胞，被称为自然杀伤细胞，通常存在于各种器官的循环和血管中，包括淋巴腺、骨髓、肝脏和肺部。令人惊讶的是，这些杀手细胞在怀孕期间在子宫内特异性地扩张，提供生长因子，帮助建立胎盘，为正在成长的胎儿提供食物。这些神奇的细胞是如何实现如此不同的功能的？其中一个决定因素是它们所处的微环境，它为这些细胞发育成杀手或建设者提供了线索。我们发现分子开关PI3K引导杀伤细胞循环。当这种分子开关被遗传或药理手段灭活时，杀伤细胞就不能正常地进入肿瘤和子宫。我们的研究计划分为三个部分，旨在：i)了解PI3K如何调节杀伤细胞从血液到组织的转变；（ii）探索杀伤细胞向肿瘤生长和转移部位迁移的机制；iii)了解PI3K如何促进杀伤细胞的胎盘构建功能及其对健康胎儿生长的影响。

A class of white blood cells specialised in sensing cancer cells and destroyomg them, known as natural killer cells, are generally found in the circulation and in blood vessels of various organs, including lymph glands, bone marrow, liver and lungs. Surprisingly, these killer cells specifically expand in the uterus during pregnancy, supplying growth factors that help to build up the placenta that feeds the growing fetus. How do these fascinating cells achieve such different functions? One deciding factor is the microenvironment they travel to, which provides cues for these cells to develop into killers or builders. We have found that the molecular switch PI3K guides killer cells in their circulation. When this molecular switch is inactivated by genetic or pharmacological means, killer cells do not traffic normally to tumours and to the uterus. Our research plan, structured in three sections, aims to: i) understand how PI3K regulates the transition of killer cells from within the blood into the tissue; (ii) explore the mechanisms of killer cell migration to the site of tumour growth and metastasis; iii) appreciate how PI3K contributes to the placenta-building function of killer cells and its consequences on healthy fetal growth.