Laboratory for Reproductive Immunology, Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai, China.
Reproduction. 2021 Jul 8;162(2):107-115. doi: 10.1530/REP-20-0639.
The T-box transcription factor protein eomesodermin (Eomes) is known for both homeostasis and function of effector and memory CD8+T cells. However, much less is known about the functional regulation of Eomes on CD8+ T cells during pregnancy. In the present study, we concluded the higher Eomes expression dCD8+T cells during normal early pregnancy. The number of Eomes+dCD8+T cells decreased in miscarriage. This Eomes+dCD8+T cell subset also expressed less growth-promoting factors, shifted toward pro-inflammatory phenotype in miscarriage. Primary Trophoblasts and HTR8/SVneo cell line could increase Eomes expression of dCD8+T cells from both normal early pregnancy and miscarriage, which might provide a new strategy for therapy to promote maternal-fetal tolerance and prevent pregnancy loss. These findings indicated that Eomes might be promising early warming targets of miscarriage. In addition, this study suggested that the reproductive safety must be a criterion considered in modulating the dose and function of Eomes in CD8+T cells to reverse T cell exhaustion.
T 盒转录因子蛋白 eomesodermin(Eomes)已知在效应器和记忆性 CD8+T 细胞的稳态和功能中起作用。然而,关于 Eomes 在怀孕期间对 CD8+T 细胞的功能调节,人们知之甚少。在本研究中,我们得出结论,正常早孕时 dCD8+T 细胞中 Eomes 表达水平较高。流产时 Eomes+dCD8+T 细胞数量减少。Eomes+dCD8+T 细胞亚群也表达较少的促生长因子,在流产时向促炎表型转变。正常早孕和流产的 dCD8+T 细胞中,滋养层细胞和 HTR8/SVneo 细胞系均可增加 Eomes 的表达,这可能为促进母胎耐受和预防妊娠丢失提供新的治疗策略。这些发现表明 Eomes 可能是流产的有前途的早期预警靶点。此外,本研究提示在调节 CD8+T 细胞中 Eomes 的剂量和功能以逆转 T 细胞耗竭时,生殖安全性必须作为一个考虑因素。