{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T19:31:21Z","timestamp":1782934281259,"version":"3.54.5"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260898"],"award-info":[{"award-number":["82260898"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20192BAB205122"],"award-info":[{"award-number":["20192BAB205122"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>This study aimed to investigate the role of regulatory T cells in patients with unexplained recurrent pregnancy loss (URPL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed 136 women who had experienced two or more miscarriages before 24\u2009weeks of gestation for no obvious reason from May 2018 to October 2021. The basic clinical data of the patients and expression of lymphocyte subsets such as regulatory T cells (Tregs) and natural killer cells (NKs) by flow cytometry were collected to explore the risk factors of pregnancy outcome in URPL patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 136 URPL patients were enrolled in this study. Eventually, 50 patients attained clinical pregnancy. The median age was 31.8\u2009\u00b1\u20094.6\u2009years in patients with clinical pregnancy. The univariate and multivariate logistic regression analyses indicated that Tregs was associated with the pregnancy outcomes of patients with URPL (odds ratio 0.63, 95% confidence interval 0.50\u20130.80). More importantly, a U-shaped association was found between Tregs and pregnancy outcome (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.001), with either higher or lower Tregs levels adversely affecting pregnancy outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tregs levels that are either too high or too low can harm pregnancy outcomes. It was expected to be a very promising quantitative biomarker for predicting pregnancy outcomes in URPL patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2023.1244424","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T04:18:06Z","timestamp":1704341886000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Overexpression of regulatory T cells in patients with unexplained recurrent pregnancy loss: friend or foe?"],"prefix":"10.3389","volume":"10","author":[{"given":"Peng-cheng","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-bin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-ping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-jiao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.fertnstert.2012.06.048","article-title":"Evaluation and treatment of recurrent pregnancy loss: a committee opinion","volume":"98","year":"2012","journal-title":"Fertil Steril"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3109\/1547691X.2014.978056","article-title":"Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA)","volume":"12","author":"Abdollahi","year":"2015","journal-title":"J Immunotoxicol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1097\/OGX.0000000000001033","article-title":"Recent advances in treatment of recurrent spontaneous abortion","volume":"77","author":"Deng","year":"2022","journal-title":"Obstet Gynecol Surv"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"eaat6114","DOI":"10.1126\/sciimmunol.aat6114","article-title":"Immune responses at the maternal-fetal interface","volume":"4","author":"Ander","year":"2019","journal-title":"Sci Immunol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"Cd000112","DOI":"10.1002\/14651858.CD000112.pub3","article-title":"Immunotherapy for recurrent miscarriage","volume":"10","author":"Wong","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/nm1452","article-title":"Decidual NK cells regulate key developmental processes at the human fetal-maternal interface","volume":"12","author":"Hanna","year":"2006","journal-title":"Nat Med"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1093\/humupd\/dmt056","article-title":"Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis","volume":"20","author":"Seshadri","year":"2014","journal-title":"Hum Reprod Update"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/ni0207-124","article-title":"Treg cells: guardians for life","volume":"8","author":"Hill","year":"2007","journal-title":"Nat Immunol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1016\/j.celrep.2019.04.109","article-title":"Three types of functional regulatory T cells control T cell responses at the human maternal-fetal Interface","volume":"27","author":"Salvany-Celades","year":"2019","journal-title":"Cell Rep"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2244","DOI":"10.1016\/j.fertnstert.2009.11.020","article-title":"Changes of CD4+ CD25 high regulatory T cells and FOXP3 expression in unexplained recurrent spontaneous abortion patients","volume":"94","author":"Mei","year":"2010","journal-title":"Fertil Steril"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.jri.2014.09.053","article-title":"Helios-positive functional regulatory T cells are decreased in decidua of miscarriage cases with normal fetal chromosomal content","volume":"107","author":"Inada","year":"2015","journal-title":"J Reprod Immunol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"103492","DOI":"10.1016\/j.jri.2022.103492","article-title":"Dynamic changes in regulatory T cells during normal pregnancy, recurrent pregnancy loss, and gestational diabetes","volume":"150","author":"Wang","year":"2022","journal-title":"J Reprod Immunol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"103694","DOI":"10.1016\/j.jri.2022.103694","article-title":"The characteristics of antigenic specificity of memory regulatory t cells in women with unexplained recurrent pregnancy loss","volume":"154","author":"Wang","year":"2022","journal-title":"J Reprod Immunol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/nri3799","article-title":"Balancing natural killer cell activation through paired receptors","volume":"15","author":"Martinet","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"939","DOI":"10.3390\/cells8080939","article-title":"Transcriptional regulation of differentiation and functions of effector T regulatory cells","volume":"8","author":"Koizumi","year":"2019","journal-title":"Cells"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1093\/intimm\/dxp095","article-title":"Regulatory T cells: how do they suppress immune responses?","volume":"21","author":"Sakaguchi","year":"2009","journal-title":"Int Immunol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"573","DOI":"10.3389\/fimmu.2019.00573","article-title":"New paradigm in the role of regulatory T cells during pregnancy","volume":"10","author":"Tsuda","year":"2019","journal-title":"Front Immunol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.jri.2018.12.002","article-title":"Effect of adoptive transfer of CD4+ CD25+ Foxp3+ Treg induced by trichostatin a on the prevention of spontaneous abortion","volume":"131","author":"Wang","year":"2019","journal-title":"J Reprod Immunol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"E422","DOI":"10.25011\/cim.v33i6.14594","article-title":"Proportional changes of CD4+ CD25+ Foxp3+ regulatory T cells in maternal peripheral blood during pregnancy and labor at term and preterm","volume":"33","author":"Xiong","year":"2010","journal-title":"Clin Invest Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jri.2011.05.006","article-title":"The unique pathophysiology of early-onset severe preeclampsia: role of decidual T regulatory cells","volume":"91","author":"Quinn","year":"2011","journal-title":"J Reprod Immunol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"5737","DOI":"10.4049\/jimmunol.180.8.5737","article-title":"Evidence for a selective migration of fetus-specific CD4+ CD25 bright regulatory T cells from the peripheral blood to the decidua in human pregnancy","volume":"180","author":"Tilburgs","year":"2008","journal-title":"J Immunol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/aji.12077","article-title":"Decidual regulatory T cells in placental pathology and pregnancy complications","volume":"69","author":"Quinn","year":"2013","journal-title":"Am J Reprod Immunol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.placenta.2005.11.008","article-title":"Differential distribution of CD4+ CD25 bright and CD8+ CD28\u2212 T-cells in decidua and maternal blood during human pregnancy","volume":"27","author":"Tilburgs","year":"2006","journal-title":"Placenta"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e13112","DOI":"10.1111\/aji.13112","article-title":"The role and mechanism of vitamin D-mediated regulation of Treg\/Th17 balance in recurrent pregnancy loss","volume":"81","author":"Ji","year":"2019","journal-title":"Am J Reprod Immunol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.4049\/jimmunol.178.4.2572","article-title":"Expansion of CD4+ CD25+ and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction","volume":"178","author":"Arruvito","year":"2007","journal-title":"J Immunol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e13551","DOI":"10.1111\/aji.13551","article-title":"Human forkhead box protein 3 gene variants associated with altered susceptibility to idiopathic recurrent pregnancy loss: a retrospective case-control study","volume":"88","author":"Bahia","year":"2022","journal-title":"Am J Reprod Immunol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"926550","DOI":"10.3389\/fimmu.2022.926550","article-title":"Emerging translational strategies and challenges for enhancing regulatory T cell therapy for graft-versus-host disease","volume":"13","author":"Hippen","year":"2022","journal-title":"Front Immunol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/nature12079","article-title":"Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota","volume":"497","author":"Cebula","year":"2013","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1002\/eji.201444480","article-title":"Foxp3+ regulatory T-cell homeostasis quantitatively differs in murine peripheral lymph nodes and spleen","volume":"45","author":"Milanez-Almeida","year":"2015","journal-title":"Eur J Immunol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/cmi.2010.45","article-title":"2-Gy whole-body irradiation significantly alters the balance of CD4+ CD25\u2212 T effector cells and CD4+ CD25+ Foxp3+ T regulatory cells in mice","volume":"7","author":"Qu","year":"2010","journal-title":"Cell Mol Immunol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e154646","DOI":"10.1172\/jci.insight.154646","article-title":"Multiplexed single-cell analysis reveals prognostic and nonprognostic T cell types in human colorectal cancer","volume":"7","author":"Masuda","year":"2022","journal-title":"JCI Insight"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/nm.4086","article-title":"Two FOXP3+ CD4+ T cell subpopulations distinctly control the prognosis of colorectal cancers","volume":"22","author":"Saito","year":"2016","journal-title":"Nat Med"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1244424\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T04:18:09Z","timestamp":1704341889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2023.1244424\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,4]]},"references-count":32,"alternative-id":["10.3389\/fmed.2023.1244424"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2023.1244424","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,4]]},"article-number":"1244424"}}