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白细胞介素-17 Vγ6 γδ T细胞在怀孕小鼠中的积累与自然流产无关。

Accumulation of IL-17 Vγ6 γδ T cells in pregnant mice is not associated with spontaneous abortion.

作者信息

Polese Barbara, Gridelet Virginie, Perrier d'Hauterive Sophie, Renard Chantal, Munaut Carine, Martens Henri, Vermijlen David, King Irah L, Jacobs Nathalie, Geenen Vincent

机构信息

GIGA-I3 Center of Immunoendocrinology GIGA Research Institute University of Liege Liege Belgium.

GIGA Laboratory of Tumor and Development Biology (LBTD) GIGA Research Institute University of Liege Liege Belgium.

出版信息

Clin Transl Immunology. 2018 Jan 29;7(1):e1008. doi: 10.1002/cti2.1008. eCollection 2018.

Abstract

INTRODUCTION

Pregnancy is an immune paradox. While the immune system is required for embryo implantation, placental development and progression of gestation, excessive inflammation is associated with pregnancy failure. Similarly, the cytokine IL-17A plays an important role in defence against extracellular pathogens, but its dysregulation can lead to pathogenic inflammation and tissue damage. Although expression of IL-17 has been reported during pregnancy, the cellular source of this cytokine and its relevance to gestation are not clear.

OBJECTIVES

Here we define the kinetics and cellular source of IL-17A in the uterus during healthy and abortion-prone murine pregnancy.

METHODS

The CBA/J x DBA/2J abortion-prone mating was used and compared to CBA/J x BALB/c control mating.

RESULTS

We demonstrate that, irrespective of gestational health, the number of IL-17-producing cells peaks during midterm pregnancy and is largely derived from the γδ T-cell lineage. We identify γδ T, Th17, CD8 T and NKT cells as the cellular source of IL-17A in pregnant mice. Furthermore, we positively identify the Vγ6 subset of uterine γδ T cells as the main producer of IL-17A during both healthy pregnancy and abortive pregnancy.

CONCLUSIONS

To conclude, the accumulation of uterine IL-17 innate-like T cells appears not to adversely impact the developing foetus. Collectively, our results show that IL-17 γδ T cells are present in the uterus throughout the course of normal gestation and therefore may play an important role in healthy pregnancy.

摘要

引言

怀孕是一种免疫悖论。虽然胚胎着床、胎盘发育和妊娠进展都需要免疫系统,但过度炎症与妊娠失败有关。同样,细胞因子白细胞介素-17A(IL-17A)在抵御细胞外病原体方面发挥着重要作用,但其失调会导致致病性炎症和组织损伤。尽管已有报道称妊娠期间会有IL-17的表达,但这种细胞因子的细胞来源及其与妊娠的相关性尚不清楚。

目的

在此,我们确定健康和易流产小鼠妊娠期间子宫中IL-17A的动力学和细胞来源。

方法

采用CBA/J×DBA/2J易流产交配组合,并与CBA/J×BALB/c对照交配组合进行比较。

结果

我们证明,无论妊娠健康状况如何,产生IL-17的细胞数量在妊娠中期达到峰值,并且主要来源于γδT细胞谱系。我们确定γδT细胞、辅助性T细胞17(Th17)、细胞毒性T细胞(CD8 T)和自然杀伤T细胞(NKT)是妊娠小鼠中IL-17A的细胞来源。此外,我们明确鉴定出子宫γδT细胞的Vγ6亚群是健康妊娠和流产妊娠期间IL-17A的主要产生者。

结论

总之,子宫中IL-17天然样T细胞的积累似乎不会对发育中的胎儿产生不利影响。总体而言,我们的结果表明,IL-17γδT细胞在正常妊娠过程中一直存在于子宫中,因此可能在健康妊娠中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/726e/5822401/5ea36e4738a5/CTI2-7-e1008-g001.jpg

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