{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T17:42:26Z","timestamp":1792345346597,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Problem<\/jats:title>\n                    <jats:p>A balanced Th1\/Th2\/Th17\/Treg status is necessary for a successful pregnancy. T cell polarization depends on the local cytokine environment and the responsiveness of T lymphocytes to cytokines. Trophoblast\u2010derived extracellular vesicles (EVs) influence the function of maternal T lymphocytes, contributing to their polarization into the Treg phenotype. We examined whether BeWo\u2010derived EVs affect T cell IL\u20106 responsiveness using the BeWo cell line as an experimental model and characterized the molecular cargo of BeWo \u2010EVs that may contribute to this process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Circulating lymphocytes from non\u2010pregnant women were treated with BeWo\u2010EVs or co\u2010cultured with BeWo cells. We detected IL\u20106R\n                      <jats:italic>\u03b1<\/jats:italic>\n                      expression by flow cytometry and IL6R signaling pathways by RT\u2010PCR. The microRNA (miRNA) content of BeWo EVs was identified by sequencing. Finally, we compared IL\u20106R\n                      <jats:italic>\u03b1<\/jats:italic>\n                      expression levels in circulating T lymphocytes from healthy pregnant and non\u2010pregnant women.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BeWo\u2010EVs reduced IL\u20106R\n                      <jats:italic>\u03b1<\/jats:italic>\n                      expression on CD4+ T cells. This modifies the IL\u20106 pathway by downregulating the transcription factors STAT3, NFKB1, and PIAS3 while upregulating STAT1. This may be due to the presence of specific microRNAs (miRNAs), such as hsa\u2010mir\u201092a\u20103p, hsa\u2010mir\u2010520f\u20103p, and hsa\u2010mir\u201025\u20103p, in BeWo\u2010EVs that target the IL\u20106 pathway. Treatment with BeWo\u2010EVs also induced phenotypic and functional changes in T cells and enhanced the ratio of CD4+\/CD25+ T cells that produce IL\u201010. Pregnancy\u2010associated IL\u20106R\n                      <jats:italic>\u03b1<\/jats:italic>\n                      downregulation has been demonstrated in clinical samples. Significantly lower levels of IL\u20106R\n                      <jats:italic>\u03b1<\/jats:italic>\n                      were detected on circulating CD4+CD25+ T cells in healthy pregnant women compared to healthy non\u2010pregnant individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our studies suggest that the microRNA content of trophoblast\u2010derived EVs significantly influences the local polarization of maternal T lymphocytes by modifying the IL\u20106R\n                      <jats:italic>\u03b1<\/jats:italic>\n                      signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.70335","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T17:30:37Z","timestamp":1792344637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BeWo\u2010Derived Extracellular Vesicles Downregulate IL\u20106R\n                    <i>\u03b1<\/i>\n                    Expression via miRNAs on CD4+ T Lymphocytes"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6558-638X","authenticated-orcid":false,"given":"G\u00e1bor","family":"Sereg\u00e9lyes","sequence":"first","affiliation":[{"name":"Institute of Genetics, Cell\u2010 and Immunobiology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"Nagy","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Cell\u2010 and Immunobiology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-160X","authenticated-orcid":false,"given":"\u00c1rp\u00e1d Ferenc","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center Semmelweis University  Budapest Hungary"},{"name":"Department of Pathology and Experimental Cancer Research Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9721-765X","authenticated-orcid":false,"given":"N\u00f3ra","family":"Fekete","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Cell\u2010 and Immunobiology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3744-206X","authenticated-orcid":false,"given":"Edit I.","family":"Buz\u00e1s","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Cell\u2010 and Immunobiology Semmelweis University  Budapest Hungary"},{"name":"MTA\u2010SE Immune\u2010Proteogenomics Extracellular Vesicle Research Group  Budapest Hungary"},{"name":"HCEMM\u2010SE Extracellular Vesicle Research Group  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5789-0951","authenticated-orcid":false,"given":"\u00c9va","family":"P\u00e1llinger","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Cell\u2010 and Immunobiology Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aan2946"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1701129114"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01302"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000527336"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/RRB.S80652"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11955"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S459263"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2023.08.065"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3464"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12613"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00891"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.14524"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2023.2284384"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2012.05.004"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.08.018"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2021.155654"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01023"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0967199422000090"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/life11101061"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1795364"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.31486\/toj.20.0049"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010023\u201001103\u20106"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010022\u201000763\u20108"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky985"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2023.07.006"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10050359"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2008.06.006"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20143457"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201023706\u20107"},{"issue":"4","key":"e_1_2_9_32_1","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1182\/blood-2010-09-307595","article-title":"Detection and Isolation of Cell\u2010Derived Microparticles Are Compromised by Protein Complexes Resulting From Shared Biophysical Parameters","volume":"117","author":"Gy\u00f6rgy B.","year":"2011","journal-title":"Blood"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201400515"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz369"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz240"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015\u20100282(02)04853\u20107"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/1933719116641760"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.649509"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/10.4.371"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.11.1303"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.140109ss"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.04.109"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01182"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)62302\u20104"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010005\u20101127\u20103"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2024.100785"},{"key":"e_1_2_9_47_1","doi-asserted-by":"crossref","unstructured":"J.Szekeres\u2010Bartho S.\u0160u\u0107urovi\u0107 andB.Mulac\u2010Jeri\u010devi\u0107 \u201cThe Role of Extracellular Vesicles and PIBF in Embryo\u2010Maternal Immune\u2010Interactions. Front Immunol \u201d9(2018 Dec 13):2890 https:\/\/doi.org\/10.3389\/fimmu.2018.02890.","DOI":"10.3389\/fimmu.2018.02890"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2011.01.014"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2014.42"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2026.1884001"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0270224"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010023\u201001150\u20106"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00604"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.06.013"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.70335","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aji.70335","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.70335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T17:30:38Z","timestamp":1792344638000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.70335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/aji.70335"],"URL":"https:\/\/doi.org\/10.1111\/aji.70335","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70335"}}