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本文引用的文献

1
Recurrent miscarriage is associated with a decline of decidual natural killer cells expressing killer cell immunoglobulin-like receptors specific for human leukocyte antigen C.复发性流产与蜕膜自然杀伤细胞数量减少有关,这些细胞表达针对人类白细胞抗原C的杀伤细胞免疫球蛋白样受体。
J Obstet Gynaecol Res. 2014 May;40(5):1288-95. doi: 10.1111/jog.12329. Epub 2014 Apr 2.
2
Therapeutic opportunities of the IL-22-IL-22R1 system.IL-22-IL-22R1 系统的治疗机会。
Nat Rev Drug Discov. 2014 Jan;13(1):21-38. doi: 10.1038/nrd4176.
3
IL-22 secreted by decidual stromal cells and NK cells promotes the survival of human trophoblasts.由蜕膜基质细胞和自然杀伤细胞分泌的白细胞介素-22可促进人滋养层细胞的存活。
Int J Clin Exp Pathol. 2013 Aug 15;6(9):1781-90. eCollection 2013.
4
IL-23: one cytokine in control of autoimmunity.IL-23:控制自身免疫的一种细胞因子。
Eur J Immunol. 2012 Sep;42(9):2263-73. doi: 10.1002/eji.201242598.
5
Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease.白细胞介素-22 可保护肠道干细胞免受免疫介导的组织损伤,并调节移植物抗宿主病的敏感性。
Immunity. 2012 Aug 24;37(2):339-50. doi: 10.1016/j.immuni.2012.05.028.
6
Evaluation and treatment of recurrent pregnancy loss: a committee opinion.复发性妊娠丢失的评估与治疗:委员会意见。
Fertil Steril. 2012 Nov;98(5):1103-11. doi: 10.1016/j.fertnstert.2012.06.048. Epub 2012 Jul 24.
7
Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage.异常胚胎染色体核型是复发性流产最常见的原因。
Hum Reprod. 2012 Aug;27(8):2297-303. doi: 10.1093/humrep/des179. Epub 2012 May 31.
8
Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion.关于 Th17 细胞与不明原因复发性自然流产关系的研究。
Am J Reprod Immunol. 2011 May;65(5):503-11. doi: 10.1111/j.1600-0897.2010.00921.x. Epub 2010 Oct 4.
9
Immature NK cells, capable of producing IL-22, are present in human uterine mucosa.能够产生白细胞介素-22的未成熟自然杀伤细胞存在于人类子宫黏膜中。
J Immunol. 2010 Oct 1;185(7):3913-8. doi: 10.4049/jimmunol.1001637. Epub 2010 Aug 27.
10
Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients.不明原因复发性自然流产患者外周血和胎盘中辅助性 T 细胞 17(Th17)细胞的比例增加。
J Reprod Immunol. 2010 Mar;84(2):164-70. doi: 10.1016/j.jri.2009.12.003. Epub 2010 Jan 27.

白细胞介素-22在早期妊娠及不明原因复发性流产患者蜕膜中的表达。

Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss.

作者信息

O'Hern Perfetto Candice, Fan Xiujun, Dahl Sabita, Krieg Sacha, Westphal Lynn Marie, Bunker Lathi Ruth, Nayak Nihar R

机构信息

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University Medical Center, 900 Welch Rd, Suite 20, Palo Alto, CA, 94304, USA,

出版信息

J Assist Reprod Genet. 2015 Jun;32(6):977-84. doi: 10.1007/s10815-015-0481-7. Epub 2015 May 1.

DOI:10.1007/s10815-015-0481-7
PMID:25925347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4491088/
Abstract

PURPOSE

Researchers have hypothesized that an imbalance of immune cells in the uterine decidua and a dysfunction in cytokines they produce may contribute to recurrent pregnancy loss (RPL). The objective of this study was to determine if IL-22, IL-23 and IL-17 are expressed abnormally in the decidua of patients with RPL compared to those women with a normal pregnancy. We also sought to confirm that uterine natural killer (uNK) cells are lower in the decidua of patients with RPL, as well as identify IL-22 expression by uNK cells.

METHODS

After meeting strict inclusion criteria, maternal decidua of nine patients with unexplained RPL and a confirmed euploid fetal loss, and 11 gestational age-matched patients undergoing elective pregnancy termination were included in our analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression, Western blot was performed to quantify protein expression and immunohistochemistry (IHC) was performed to identify IL-22 and uNK cells.

RESULTS

We found that women with unexplained RPL and a euploid fetal loss had significantly less gene and protein expression of IL-22 in the decidua. Additionally, we found that IL-22 is primarily expressed by uNK cells in the decidua.

CONCLUSIONS

In conclusion, our results suggest that lower levels of IL-22 in the uterine decidua in patients with unexplained RPL may contribute to a disruption of decidual homeostasis and ultimately lead to early pregnancy loss.

摘要

目的

研究人员推测,子宫蜕膜中免疫细胞失衡及其产生的细胞因子功能障碍可能导致复发性流产(RPL)。本研究的目的是确定与正常妊娠女性相比,RPL患者蜕膜中白细胞介素-22(IL-22)、白细胞介素-23(IL-23)和白细胞介素-17(IL-17)的表达是否异常。我们还试图证实RPL患者蜕膜中的子宫自然杀伤(uNK)细胞数量较少,并确定uNK细胞中IL-22的表达情况。

方法

在满足严格的纳入标准后,我们分析纳入了9例原因不明的RPL且确诊为整倍体胎儿丢失患者的母体蜕膜,以及11例孕龄匹配的接受选择性妊娠终止的患者。采用定量实时聚合酶链反应(qRT-PCR)定量RNA表达,采用蛋白质免疫印迹法定量蛋白质表达,并采用免疫组织化学(IHC)鉴定IL-22和uNK细胞。

结果

我们发现,原因不明的RPL且整倍体胎儿丢失的女性蜕膜中IL-22的基因和蛋白质表达显著降低。此外,我们发现IL-22主要由蜕膜中的uNK细胞表达。

结论

总之,我们的结果表明,原因不明的RPL患者子宫蜕膜中IL-22水平较低可能导致蜕膜内环境稳态破坏,最终导致早期妊娠丢失。