Stefanie Dietz-Ziegler, Samantha Kewitz, Gabriele Kaiser, Jessica Rühle, Alexander Marmé, Alexander Dalpke, Bachar Cheaib, Jan Pauluschke-Fröhlich, Melanie Henes, Ana Velic, Andreas Pich, Anneli Vollert, Martin Schaller, Felix Knab, Trim Lajqi, Christian F. Poets, Christian Gille, Natascha Köstlin-Gille
{"title":"来自孕妇粪便的细胞外囊泡在体外调节T细胞向妊娠支持表型。","authors":"Stefanie Dietz-Ziegler, Samantha Kewitz, Gabriele Kaiser, Jessica Rühle, Alexander Marmé, Alexander Dalpke, Bachar Cheaib, Jan Pauluschke-Fröhlich, Melanie Henes, Ana Velic, Andreas Pich, Anneli Vollert, Martin Schaller, Felix Knab, Trim Lajqi, Christian F. Poets, Christian Gille, Natascha Köstlin-Gille","doi":"10.1002/eji.70056","DOIUrl":null,"url":null,"abstract":"<p>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 <i>in vitro</i>. fEVs were purified from preserved stool samples, characterized, and their uptake by immune cells was analyzed. Using an <i>in vitro</i> 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 <i>in vitro</i> 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.</p>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 9","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.70056","citationCount":"0","resultStr":"{\"title\":\"Extracellular Vesicles Derived From the Feces of Pregnant Women Modulate T Cells Toward a Pregnancy-Supportive Phenotype In Vitro\",\"authors\":\"Stefanie Dietz-Ziegler, Samantha Kewitz, Gabriele Kaiser, Jessica Rühle, Alexander Marmé, Alexander Dalpke, Bachar Cheaib, Jan Pauluschke-Fröhlich, Melanie Henes, Ana Velic, Andreas Pich, Anneli Vollert, Martin Schaller, Felix Knab, Trim Lajqi, Christian F. 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Extracellular Vesicles Derived From the Feces of Pregnant Women Modulate T Cells Toward a Pregnancy-Supportive Phenotype In Vitro
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.
期刊介绍:
The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.