CD4 + CD25 + Tregs的过继转移可部分缓解小鼠卵巢早衰。,Molecular Reproduction and Development

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CD4 + CD25 + Tregs的过继转移可部分缓解小鼠卵巢早衰。
Molecular Reproduction and Development ( IF 2.7 ) Pub Date : 2020-08-01 , DOI: 10.1002/mrd.23404
Dan Liu _{1,

2} , Xiaojuan Tu ₁ , Chuanmengyuan Huang _{1,

2} , Yuncang Yuan ₁ , Ying Wang ₁ , Xiaona Liu ₁ , Wei He ₁

Affiliation

这项研究旨在研究CD4 ⁺ CD25 ⁺调节性T细胞（Treg）对透明带糖蛋白3肽（pZP3）免疫诱导的小鼠卵巢早衰（POI）的保护作用。通过两次皮下注射pZP3（50 nmol / L）诱导出小鼠POI模型。pZP3-Treg组的小鼠腹膜内注射5×10 ⁵ CD4 ⁺ CD25 ⁺POI模型建立后的Treg。评估卵巢中的性激素水平，卵泡数目，凋亡事件和Akt / FOXO3a信号通路分子。与对照组相比，pZP3组和pZP3-Treg组的卵巢重量均降低，两者之间无差异。与对照组相比，Treg转移小鼠中的卵泡数量与对照组相比明显减少，但与单独的pZP3组相比却显示出适度的改善。血清中促卵泡激素，促黄体生成素和抗透明质酸抗体（AZPAbs）的血清浓度显着降低，而雌二醇和抗穆勒激素的浓度却升高。在机制上，将Treg细胞转移至ZP3处理的小鼠后，将Caspase3的水平恢复至控制水平，而部分还原的Bax对Bcl-2没有影响。此外，将Treg细胞转移至ZP3处理的小鼠后，部分恢复了Akt和FOXO3a的水平，部分恢复了p-Akt / Akt和p-FOXO3a / FOXO3a的比率。总之，Treg细胞改善了ZP3诱导的POI的某些方面，这些方面可能是通过抑制卵巢细胞凋亡并参与Akt / FOXO3a信号传导途径来介导的。因此，Treg细胞可能对自身免疫性POI具有保护作用。

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Adoptive transfers of CD4+ CD25+ Tregs partially alleviate mouse premature ovarian insufficiency.

This study was designed to investigate the protective effect of CD4⁺CD25⁺ regulatory T cells (Tregs) against zona pellucida glycoprotein 3 peptide (pZP3) immunization‐induced premature ovarian insufficiency (POI) in mice. A mouse POI model was induced by two subcutaneous injections of pZP3 (50 nmol/L). Mice in the pZP3‐Treg group were intraperitoneally injected with 5 × 10⁵ CD4⁺CD25⁺ Tregs after the POI model was established. Sex hormone levels, follicle numbers, apoptotic events, and the Akt/FOXO3a signaling pathway molecules in the ovaries were assessed. Compared with control group, the weight of ovaries in both pZP3 group and pZP3‐Treg group was decreased and no difference was found between them. The number of follicles in the Treg transferred mice, like in pZP3 group, was significantly reduced compared to the control group, but showed a modest improvement when compared the pZP3 group alone. Significantly lower serum concentrations of follicle‐stimulating hormone, luteinizing hormone, and anti‐zona pellucida antibodies (AZPAbs) were found, while the concentrations of estradiol and anti‐Mullerian hormone increased. In mechanism, Treg cell transfer to ZP3 treated mice restored the levels of Caspase3 to control levels, and partially restored Bax, however, had no effect on Bcl‐2. Moreover, Treg cell transfer to ZP3 treated mice partially restored the levels of Akt and FOXO3a, and partially restored the ratios of p‐Akt/Akt and p‐FOXO3a/FOXO3a. In conclusion, Treg cells improved some aspects of ZP3‐induced POI which may be mediate by suppressing ovarian cells apoptosis and involving the Akt/FOXO3a signaling pathway. Therefore, Treg cells may be protective against autoimmune POI.

更新日期：2020-08-28

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