Department of Neonatology, Tuebingen University Children's Hospital, Tuebingen, Germany.
Interfaculty Institute for Cell Biology, Proteome Center Tuebingen (PCT), University of Tuebingen, Tübingen, Germany.
Front Immunol. 2022 Jan 17;12:787468. doi: 10.3389/fimmu.2021.787468. eCollection 2021.
During pregnancy, maternal immune system has to balance tightly between protection against pathogens and tolerance towards a semi-allogeneic organism. Dysfunction of this immune adaptation can lead to severe complications such as pregnancy loss, preeclampsia or fetal growth restriction. In the present study we analyzed the impact of the murine MHC class Ib molecule Qa-2 on pregnancy outcome . We demonstrate that lack of Qa-2 led to intrauterine growth restriction and increased abortion rates especially in late pregnancy accompanied by a disturbed trophoblast invasion and altered spiral artery remodeling as well as protein aggregation in trophoblast cells indicating a preeclampsia-like phenotype. Furthermore, lack of Qa-2 caused imbalanced immunological adaptation to pregnancy with altered immune cell and especially T-cell homeostasis, reduced T numbers and decreased accumulation and functional activation of myeloid-derived suppressor cells. Lastly, we show that application of sHLA-G reduced abortion rates in Qa-2 deficient mice by inducing MDSC. Our results highlight the importance of an interaction between HLA-G and MDSC for pregnancy success and the therapeutic potential of HLA-G for treatment of immunological pregnancy complications.
在怀孕期间，母体免疫系统必须在防止病原体和耐受半同种异体生物之间保持紧密平衡。这种免疫适应的功能障碍可导致严重并发症，如流产、先兆子痫或胎儿生长受限。在本研究中，我们分析了小鼠 MHC 类 Ib 分子 Qa-2 对妊娠结局的影响。我们证明缺乏 Qa-2 会导致宫内生长受限和流产率增加，尤其是在妊娠晚期，伴有滋养层浸润紊乱、螺旋动脉重塑改变以及滋养层细胞中蛋白聚集，表明存在先兆子痫样表型。此外，缺乏 Qa-2 导致对妊娠的免疫适应性失衡，免疫细胞特别是 T 细胞平衡受到干扰，T 细胞数量减少，髓源抑制细胞的积累和功能激活减少。最后，我们表明，sHLA-G 的应用通过诱导 MDSC 降低了 Qa-2 缺陷小鼠的流产率。我们的研究结果强调了 HLA-G 与 MDSC 之间相互作用对妊娠成功的重要性，以及 HLA-G 治疗免疫性妊娠并发症的治疗潜力。
