Dietz-Ziegler Stefanie, Kewitz Samantha, Kaiser Gabriele, Rühle Jessica, Marmé Alexander, Dalpke Alexander, Cheaib Bachar, Pauluschke-Fröhlich Jan, Henes Melanie, Velic Ana, Pich Andreas, Vollert Anneli, Schaller Martin, Knab Felix, Lajqi Trim, Poets Christian F, Gille Christian, Köstlin-Gille Natascha
Department of Neonatology, Tuebingen University Children's Hospital, Tuebingen, Germany.
Department of Neonatology, Heidelberg University Children's Hospital, Heidelberg, Germany.
Eur J Immunol. 2025 Sep;55(9):e70056. doi: 10.1002/eji.70056.
Pregnancy requires immune tolerance to a semi-allogeneic fetus, involving profound adaptations, particularly in the T helper (Th) cell response. The intestinal microbiome plays a crucial role in health, but its influence on immune adaptation to pregnancy remains unclear. Bacterial extracellular vesicles (BEVs), released by gut bacteria, can cross the intestinal barrier and modulate immune responses. In our study we investigated the effect of fecal EVs (fEVs) from pregnant women on Th cell composition in vitro. fEVs were purified from preserved stool samples, characterized, and their uptake by immune cells was analyzed. Using an in vitro T cell culture model, we examined Th cell phenotypes, intracellular cytokine expression, and proteomic changes after stimulation with fEVs from pregnant and non-pregnant women. We demonstrate that fEVs from preserved stool samples are rapidly taken up by T cells and modulate their phenotype. Stimulation with fEVs from pregnant women shifts Th cells toward a regulatory profile favorable for pregnancy, increasing Th2 cells while reducing Th17 cells compared to fEVs from non-pregnant controls. This study provides the first in vitro evidence that fecal-derived EVs influence immune adaptation to pregnancy and may offer a basis for microbiome-targeted strategies to prevent or treat immunological pregnancy complications.
怀孕需要对半同种异体胎儿产生免疫耐受，这涉及深刻的适应性变化，尤其是在辅助性T（Th）细胞反应方面。肠道微生物群在健康中起着至关重要的作用，但其对孕期免疫适应的影响仍不清楚。肠道细菌释放的细菌细胞外囊泡（BEV）可穿过肠道屏障并调节免疫反应。在我们的研究中，我们调查了孕妇粪便细胞外囊泡（fEV）对体外Th细胞组成的影响。从保存的粪便样本中纯化fEV，对其进行表征，并分析免疫细胞对它们的摄取情况。使用体外T细胞培养模型，我们检测了用孕妇和非孕妇的fEV刺激后Th细胞表型、细胞内细胞因子表达和蛋白质组学变化。我们证明，来自保存粪便样本的fEV能被T细胞迅速摄取并调节其表型。与非孕妇对照组的fEV相比，用孕妇的fEV刺激可使Th细胞向有利于怀孕的调节性表型转变，增加Th2细胞，同时减少Th17细胞。这项研究提供了首个体外证据，表明粪便来源的EV会影响对怀孕的免疫适应，并可能为预防或治疗免疫性妊娠并发症的微生物群靶向策略提供依据。
