BIOLOGY OF HUMAN UTERINE NK CELLS

人类子宫 NK 细胞的生物学

• 批准号: 6696294
• 负责人: ASHLEY Moffett
• 金额: $ 15.58万
• 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 2005-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6696294
• 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植入和发育取决于子宫内膜从子宫内膜到蜕膜的转变。 蜕膜的形成对于正常妊娠至关重要。 在非怀孕周期中，子宫内膜会在月经时分解，类似的过程也会发生在流产时失败的妊娠中。 导致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。 这一提议的假设是，子宫粘膜白细胞的异常群体，即子宫自然杀伤（NK）细胞，在分泌性子宫内膜必须做出蜕膜或月经的关键决定中发挥着关键作用。 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为丰富，并且它们是蜕膜的组成部分。在非妊娠周期中，它们在月经中断前 2-3 天经历细胞凋亡，然后没有月经的其他形态特征。 具体问题是：1）子宫粘膜中的NK细胞是从血液中招募的吗？ 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细胞可以影响蜕膜化过程吗？这项工作将增进对人类生殖生理学中两个关键过程——蜕膜化和月经的理解。因此，这项工作将对妇女的健康产生重大影响。它可以为多种疾病带来新的治疗方法，包括不孕症、流产、胎盘缺陷引起的疾病（先兆子痫和IUGR）和月经失调。

项目成果

Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success.

母体KIR和胎儿HLA-C基因的组合会影响先兆子痫和生殖成功的风险。

• DOI: 10.1084/jem.20041214
• 发表时间: 2004-10-18
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Hiby, SE;Walker, JJ;O'Shaughnessy, KM;Redman, CWG;Carrington, M;Trowsdale, J;Moffett, A
• 通讯作者: Moffett, A

Maternal KIR in combination with paternal HLA-C2 regulate human birth weight.

• DOI: 10.4049/jimmunol.1400577
• 发表时间: 2014-06-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Hiby SE;Apps R;Chazara O;Farrell LE;Magnus P;Trogstad L;Gjessing HK;Carrington M;Moffett A
• 通讯作者: Moffett A

Molecular characterization of KIR3DL3.

KIR3DL3 的分子表征。

• DOI: 10.1007/s00251-005-0060-7
• 发表时间: 2006
• 期刊: Immunogenetics
• 影响因子: 3.2
• 作者: Trundley,AnitaE;Hiby,SusanE;Chang,Chiwen;Sharkey,AndrewM;Santourlidis,Simeon;Uhrberg,Markus;Trowsdale,John;Moffett,Ashley
• 通讯作者: Moffett,Ashley