Adoptive transfer of pregnancy-induced CD4CD25 regulatory T cells reverses the increase in abortion rate caused by interleukin 17 in the CBA/JBALB/c mouse model

作者：Wang, Wen-Juan^*; Liu, Fu-Jun; Xin-Liu; Hao, Cui-Fang; Bao, Hong-Chu; Qu, Qing-Lan; Liu, Xue-Mei

来源：Human Reproduction, 2014, 29(5): 946-952.

DOI：10.1093/humrep/deu014

• interleukin-17
• regulatory T cells
• pregnancy
• miscarriage

Could adoptive transfer of pregnancy-induced CD4CD25 regulatory T cells (Tregs) reverse the increase in abortion rate caused by interleukin 17 (IL-17) in the CBA/J BALB/c mouse model?
The effects of exogenous IL-17 on increased abortion rate, as well as decreased transforming growth factor (TGF)- and IL-10 expression, are reversed by a pre-mating transfusion of Tregs in a mouse model of pregnancy.
IL-17 is a pro-inflammatory cytokine mainly expressed by T helper 17 cells, and plays a pivotal role in the pathogenesis of endometriosis, miscarriage, preterm labor and pre-eclampsia. The activity of Th17 cells is attenuated by the anti-inflammatory action of Tregs.
Fifty microliters of phosphate-buffered saline (PBS) (Group 1,) or recombinant IL-17 (rIL) (10 g/mouse) supernatant (Group 2) was administered in the vaginal vaults of anesthetized pregnant CBA/J mice on Day 1 of pregnancy. Tregs (2 10(5) cells) purified from pregnant CBA/J BALB/c mice were given i.v. via the tail vein 2 days before mating (Group 3) or on Day 7 of pregnancy (Group 4).
Mice (n 40) were randomly assigned to one of four experimental groups. The numbers of surviving and reabsorbed fetuses in each group were counted on Day 14 of pregnancy, and the expression of interferon (IFN)-, IL-4, TGF- and IL-10 in the decidual tissue was assessed by real-time RTPCR and western blotting.
Normal pregnant CBA/J mice mated with BALB/c males which received transvaginal rIL-17 presented with a significantly increased abortion rate compared with the group which received PBS (27.7 versus 9.9, respectively; P 0.05). The transfusion of pregnancy-induced Tregs from 14-day normal pregnant mice 2 days before mating reduced the abortion rate caused by IL-17 (12.5 versus 27.7, respectively; P 0.05), while transfusion of Tregs on Day 7 of pregnancy had no effect. Transfusion of Tregs did not affect IFN- or IL-4 expression in the decidual tissue at either the mRNA or protein level. Administration of rIL-17 resulted in a decrease in production of TGF- and IL-10 at both mRNA and protein levels (P 0.05). Transfusion of Tregs before mating increased TGF- and IL-10 mRNA and protein levels (P 0.05), while Tregs transfusion at Day 7 of pregnancy had no effect on TGF- or IL-10 expression.
These data derive from only a small number of mice. It is unclear whether the same effects would be seen in humans.
Abnormally elevated expression of IL-17 in the feto-maternal interface may result in miscarriage. Transfer of antigen-specific Tregs before mating takes place may have potential applications in the prevention of recurrent spontaneous abortion.
This work was supported by a grant from the National Natural Science Foundation of China (81370013, 81000277 and 81300533) and Shandong Provincial Natural Science Foundation, China (ZR2013HQ002). There were no conflicts of interest.

• 出版日期2014-5
• 单位烟台毓璜顶医院; 青岛大学