BIOLOGY OF HUMAN UTERINE NK CELLS

人类子宫 NK 细胞的生物学

• 批准号: 6225406
• 负责人: ASHLEY Moffett
• 金额: $ 18.06万
• 依托单位: UNIVERSITY OF CAMBRIDGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-21 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6225406
• 关键词: apoptosis; cell differentiation; cell growth regulation; cell migration; decidua; human tissue; menstrual cycle; natural killer cells; uterus

In human pregnancy normal implantation and development of the feto-placental unit is dependent on transformation of the uterine lining from endometrium to decidua. The formation of decidua is essential for normal pregnancy. In a non-pregnant cycle the endometrium breaks down at menstruation and a similar process occurs in a failing pregnancy at miscarriage. The cellular and molecular processes responsible for formation of decidua or endometrial breakdown are largely unknown. The hypothesis underlying this proposal is that the unusual population of uterine mucosal leucocytes, uterine Natural Killer (N K) cells, play a pivotal role in the critical decision that the secretory endometrium must make either to decidualise or undergo menstruation. The functions of uterine NK cells are unknown, but they are most abundant in species which undergo mucosal decidualisation and they are an integral part of decidua. In non-pregnant cycles they undergo apoptosis 2-3 days preceding menstrual breakdown before there are no other morphological features of menstruation. The specific questions are: 1) Are the NK cells in the uterine mucosa recruited from the blood? 2) What factors in the uterine microenvironment are responsible for triggering NK cell apoptosis or maintaining NK cell survival? 3) Can uterine NK cells influence the process of decidualisation? This work will increase understanding of two crucial processes in human reproductive physiology - decidualisation and menstruation. Therefore this work will have a major impact on women's health. It could lead to novel therapeutic approaches in a wide range of disorders including infertility, miscarriage, disorders due to defective placentation (pre-eclampsia and IUGR) and menstrual disorders.

在人类妊娠中，胎儿-胎盘单位的正常着床和发育依赖于子宫内膜向蜕膜的转化。 蜕膜的形成对正常妊娠是必不可少的。 在非妊娠周期中，子宫内膜在月经时破裂，类似的过程发生在流产时的妊娠失败中。 蜕膜形成或子宫内膜破裂的细胞和分子过程在很大程度上是未知的。 这一假设的基础是，子宫粘膜白细胞，子宫自然杀伤（NK）细胞的不寻常的人口，在分泌期子宫内膜必须作出的决定，无论是蜕膜化或经历月经的关键作用。 子宫NK细胞的功能尚不清楚，但它们在经历粘膜蜕膜化的物种中最丰富，并且它们是蜕膜的组成部分。在非妊娠周期中，它们在月经崩溃前2-3天发生凋亡，然后没有月经的其他形态学特征。 具体问题是：1）子宫粘膜中的NK细胞是否从血液中募集？2)子宫微环境中的哪些因素负责触发NK细胞凋亡或维持NK细胞存活？3)子宫NK细胞能影响蜕膜化过程吗？这项工作将增加对人类生殖生理学中两个关键过程的理解-蜕膜化和月经。因此，这项工作将对妇女健康产生重大影响。它可能会导致新的治疗方法，在广泛的疾病，包括不孕症，流产，疾病，由于有缺陷的胎盘（先兆子痫和IUGR）和月经失调。