{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:05:55Z","timestamp":1780578355719,"version":"3.54.1"},"reference-count":80,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Immune tolerance at the feto-maternal interface is crucial for the growth of the semi-allograft fetus in the womb. The outcome of pregnancy is dependent on a fine balance between various immunological forces. For a long time, the potential role of the immune system in pregnancy disorders has remained enigmatic. Current evidence has revealed that natural killer (NK) cells are the predominant immune cell population in the uterine decidua. NK cells cooperate with T-cells to provide an optimal microenvironment for the growth of the developing fetus by producing cytokines, chemokines, and angiogenic factors. These factors support trophoblast migration and angiogenesis which regulates the process of placentation. NK cells differentiate between \u201cself\u201d and \u201cnon-self\u201d through their surface receptors known as killer-cell immunoglobulin-like receptors (KIRs). They induce immune tolerance through communication via their KIR and fetal human leucocyte antigens (HLA). KIRs are surface receptors of NKs that comprise both activating and inhibiting receptors. Due to the wide diversity manifested by its genes, the KIR repertoire is different in each individual. Significant evidence has implicated KIRs in recurrent spontaneous abortion (RSA); however, maternal KIR gene diversity in RSA is still unclear. Research has shown that immunological aberrancies including activating KIRs, NK abnormalities, and T cell downregulation are risk factors for RSA. In this review, we discuss relevant data from experimental studies on NK cell abnormalities, KIR, and T-cells in the incidence of recurrent spontaneous abortion.<\/jats:p>","DOI":"10.3390\/jcm12041355","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T01:37:07Z","timestamp":1675906627000},"page":"1355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Recurrent Abortion and the Involvement of Killer-Cell Immunoglobulin-like Receptor (KIR) Genes, Activated T Cells, NK Abnormalities, and Cytokine Profiles"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0532-7929","authenticated-orcid":false,"given":"Mihaela","family":"Andreescu","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Hematology, Faculty of Medicine, Titu Maiorescu University of Bucharest, 040051 Bucharest, Romania"},{"name":"Department of Hematology, Colentina Clinical Hospital, 020125 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2746-6153","authenticated-orcid":false,"given":"Francesca","family":"Fr\u00eencu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, 01171 Bucharest, Romania"},{"name":"Department of Obstetrics and Gynecology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0931-0596","authenticated-orcid":false,"given":"Mihaela","family":"Plotogea","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nicolae Malaxa Clinical Hospital, 022441 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Mehedin\u021bu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Filantropia Clinical Hospital, 01171 Bucharest, Romania"},{"name":"Department of Obstetrics and Gynecology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/j.1600-0897.2010.00810.x","article-title":"Interleukin-10: A Multi-Faceted Agent of Pregnancy","volume":"63","author":"Thaxton","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.4049\/jimmunol.1202698","article-title":"Human Chorionic Gonadotropin as a Central Regulator of Pregnancy Immune Tolerance","volume":"190","author":"Schumacher","year":"2013","journal-title":"J. Immunol."},{"key":"ref_3","unstructured":"Blue, N.R., Page, J.M., and Silver, R.M. (2019). Seminars in Perinatology, Elsevier."},{"key":"ref_4","first-page":"139","article-title":"Environmental factors in declining human fertility","volume":"18","author":"Levine","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nri.2017.64","article-title":"The unique immunological and microbial aspects of pregnancy","volume":"17","author":"Mor","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114316","DOI":"10.1016\/j.bcp.2020.114316","article-title":"Detection of Viral Infections by Innate Immunity","volume":"183","author":"Carty","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Murata, H., Tanaka, S., and Okada, H. (2021). Immune Tolerance of the Human Decidua. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020351"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.3389\/fimmu.2019.02729","article-title":"Editorial: Fetal-Maternal Immune Interactions in Pregnancy","volume":"10","author":"Than","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.3389\/fimmu.2020.01023","article-title":"Role of Regulatory T Cells in Regulating Fetal-Maternal Immune Tolerance in Healthy Pregnancies and Reproductive Diseases","volume":"11","author":"Huang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fimmu.2013.00008","article-title":"Killer Cell Immunoglobulin-Like Receptor Gene Associations with Autoimmune and Allergic Diseases, Recurrent Spontaneous Abortion, and Neoplasms","volume":"4","author":"Kusnierczyk","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/ajmg.a.32058","article-title":"Cytogenetic study of spontaneous abortions using semi-direct analysis of chorionic villi samples detects the broadest spectrum of chromosome abnormalities","volume":"146A","author":"Morales","year":"2007","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hu, X., Miao, M., Bai, Y., Cheng, N., and Ren, X. (2018). Reproductive Factors and Risk of Spontaneous Abortion in the Jinchang Cohort. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15112444"},{"key":"ref_13","first-page":"197","article-title":"Recurrent Spontaneous Abortion (RSA) and Maternal KIR Genes: A Comprehensive Meta-Analysis","volume":"24","author":"Akbari","year":"2020","journal-title":"JBRA Assist. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3303","DOI":"10.1007\/s43032-021-00599-y","article-title":"The Role of Immune Cells in Recurrent Spontaneous Abortion","volume":"28","author":"Li","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1055\/s-0036-1582397","article-title":"Inflammation in Complicated Pregnancy and Its Outcome","volume":"33","author":"Kalagiri","year":"2016","journal-title":"Am. J. Perinatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/jog.13799","article-title":"Obesity and recurrent miscarriage: A systematic review and meta-analysis","volume":"45","author":"Cavalcante","year":"2018","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/cmi.2014.54","article-title":"TH17 cells in human recurrent pregnancy loss and pre-eclampsia","volume":"11","author":"Fu","year":"2014","journal-title":"Cell. Mol. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1016\/j.fertnstert.2009.11.020","article-title":"Changes of CD4+CD25high regulatory T cells and FOXP3 expression in unexplained recurrent spontaneous abortion patients","volume":"94","author":"Mei","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1600-0897.2010.00836.x","article-title":"The Immune System in Pregnancy: A Unique Complexity","volume":"63","author":"Mor","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1016\/j.fertnstert.2007.05.064","article-title":"Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates","volume":"89","author":"Zhou","year":"2008","journal-title":"Fertil. Steril."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1196\/annals.1434.006","article-title":"Inflammation and pregnancy: The role of toll-like receptors in trophoblast-immune interaction","volume":"1127","author":"Mor","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0001-706X(03)00097-4","article-title":"The epidemiology and consequences of maternal malaria: A review of immunological basis","volume":"87","author":"Okoko","year":"2003","journal-title":"Acta Trop."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/BF00048565","article-title":"Natural killer cells: Artifact to reality: An odyssey in biology","volume":"2","author":"Oldham","year":"1983","journal-title":"Cancer Metastasis Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.3389\/fimmu.2018.01869","article-title":"Natural Killer Cells: Development, Maturation, and Clinical Utilization","volume":"9","author":"Abel","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1600-0897.2008.00595.x","article-title":"REVIEW ARTICLE: Evolution of Non-Cytotoxic Uterine Natural Killer Cells","volume":"59","author":"Kalkunte","year":"2008","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.semcancer.2006.07.005","article-title":"Tumor and viral recognition by natural killer cells receptors","volume":"16","author":"Arnon","year":"2006","journal-title":"Semin. Cancer Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1111\/jog.13448","article-title":"Expression of natural cytotoxicity receptors and cytokine production on endometrial natural killer cells in women with recurrent pregnancy loss or implantation failure, and the expression of natural cytotoxicity receptors on peripheral blood natural kille","volume":"43","author":"Fukui","year":"2017","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1387\/ijdb.140109ss","article-title":"Natural killer cells and regulatory T cells in early pregnancy loss","volume":"58","author":"Sharma","year":"2014","journal-title":"Int. J. Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jri.2003.09.002","article-title":"Role of a KIR\/HLA-C allorecognition system in pregnancy","volume":"62","year":"2004","journal-title":"J. Reprod. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1600-0897.2007.00524.x","article-title":"Increased Natural Killer Cell Cytotoxicity and IL-2 Production in Recurrent Spontaneous Abortion","volume":"58","author":"Hadinedoushan","year":"2007","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1034\/j.1600-0897.2003.00095.x","article-title":"Pre-conceptional Natural Killer Cell Activity and Percentage as Predictors of Biochemical Pregnancy and Spontaneous Abortion with Normal Chromosome Karyotype","volume":"50","author":"Yamada","year":"2003","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jri.2012.06.005","article-title":"Enhancement of peripheral blood CD56dim cell and NK cell cytotoxicity in women with recurrent spontaneous abortion or in vitro fertilization failure","volume":"95","author":"Karami","year":"2012","journal-title":"J. Reprod. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/S0015-0282(03)00611-3","article-title":"Differences in number and activity of peripheral natural killer cells in primary versus secondary recurrent miscarriage","volume":"80","author":"Shakhar","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.8755-8920.2001.460203.x","article-title":"High NK Cell Activity in Early Pregnancy Correlates with Subsequent Abortion with Normal Chromosomes in Women with Recurrent Abortion","volume":"46","author":"Yamada","year":"2001","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1600-0897.2005.00356.x","article-title":"High Levels of Peripheral Blood NK Cells in Women Suffering from Recurrent Spontaneous Abortion are Reverted from High-Dose Intravenous Immunoglobulins","volume":"55","author":"Perricone","year":"2006","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/j.1600-0897.2006.00431.x","article-title":"Expression of Natural Cytotoxicity Receptors and a2V-ATPase on Peripheral Blood NK Cell Subsets in Women with Recurrent Spontaneous Abortions and Implantation Failures","volume":"56","author":"Fukui","year":"2006","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/j.1600-0897.2006.00465.x","article-title":"The relationship of systemic TNF-alpha and IFN-gamma with IVF treatment outcome and peripheral blood NK cells","volume":"57","author":"Thum","year":"2007","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1093\/humrep\/16.5.855","article-title":"Status of peripheral blood natural killer cells in women with recurrent spontaneous abortions and infertility of unknown aetiology","volume":"16","author":"Ntrivalas","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1034\/j.1600-0897.2002.01060.x","article-title":"Deficiency of Decidual IL-10 in First Trimester Missed Abortion: A Lack of Correlation with the Decidual Immune Cell Profile","volume":"47","author":"Plevyak","year":"2002","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_40","first-page":"230742","article-title":"Interleukin 10 and Tumor Necrosis Factor-Alpha in Pregnancy: Aspects of Interest in Clinical Obstetrics","volume":"2012","author":"Moreli","year":"2012","journal-title":"ISRN Obstet. Gynecol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"BSR20170150","DOI":"10.1042\/BSR20170150","article-title":"Simultaneous detection of decidual Th1\/Th2 and NK1\/NK2 immunophenotyping in unknown recurrent miscarriage using 8-color flow cytometry with FSC\/Vt extended strategy","volume":"37","author":"Dong","year":"2017","journal-title":"Biosci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/j.fertnstert.2015.08.011","article-title":"Role of inflammatory mediators in patients with recurrent pregnancy loss","volume":"104","author":"Comba","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_43","first-page":"1781","article-title":"IL-22 secreted by decidual stromal cells and NK cells promotes the survival of human trophoblasts","volume":"6","author":"Wang","year":"2013","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_44","first-page":"248","article-title":"Deciphering the killer-cell immunoglobulin-like receptor system at super-resolution for natural killer and T-cell biology","volume":"150","author":"Hilton","year":"2016","journal-title":"Immunology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1365-2567.2009.03208.x","article-title":"The extensive polymorphism of KIR genes","volume":"129","author":"Middleton","year":"2009","journal-title":"Immunology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2174\/1874226200801010042","article-title":"Different Evolution of Inhibitory and Activating Killer Immunoglobulin Receptors (KIR) in Worldwide Human Populations","volume":"1","author":"Middleton","year":"2008","journal-title":"Open Immunol. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1034\/j.1600-065X.2002.19004.x","article-title":"The killer cell immunoglobulin-like receptor (KIR) genomic region: Gene-order, haplotypes and allelic polymorphism","volume":"190","author":"Hsu","year":"2002","journal-title":"Immunol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1146\/annurev.genom.7.080505.115726","article-title":"The Killer Immunoglobulin-Like Receptor Gene Cluster: Tuning the Genome for Defense","volume":"7","author":"Bashirova","year":"2006","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.coi.2012.01.001","article-title":"NK cell MHC class I specific receptors (KIR): From biology to clinical intervention","volume":"24","author":"Thielens","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1101\/gr.137976.112","article-title":"Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors","volume":"22","author":"Jiang","year":"2012","journal-title":"Genome Res."},{"key":"ref_51","first-page":"194","article-title":"The relationship of maternal KIR and parental HLA-C genes with risk of recurrent spontaneous abortion: A regional study in Lorestan Province, Iran","volume":"5","author":"Akbari","year":"2018","journal-title":"Crescent J. Med. Biol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.bbrc.2007.06.125","article-title":"Increased activating killer immunoglobulin-like receptor genes and decreased specific HLA-C alleles in couples with recurrent spontaneous abortion","volume":"360","author":"Wang","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1093\/humrep\/den011","article-title":"Association of maternal killer-cell immunoglobulin-like receptors and parental HLA-C genotypes with recurrent miscarriage","volume":"23","author":"Hiby","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1093\/humrep\/deh483","article-title":"Maternal KIR repertoire is not associated with recurrent spontaneous abortion","volume":"19","author":"Witt","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1111\/jog.12329","article-title":"Recurrent miscarriage is associated with a decline of decidual natural killer cells expressing killer cell immunoglobulin-like receptors specific for human leukocyte antigen C","volume":"40","author":"Wang","year":"2014","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1600-0897.2004.00139.x","article-title":"Decrease in a Specific Killer Cell Immunoglobulin-Like Receptor on Peripheral Natural Killer Cells in Women with Recurrent Spontaneous Abortion of Unexplained Etiology","volume":"51","author":"Yamada","year":"2004","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.humimm.2004.10.005","article-title":"Lack of the appropriate natural killer cell inhibitory receptors in women with spontaneous abortion","volume":"66","author":"Keramitsoglou","year":"2005","journal-title":"Hum. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/aji.12453","article-title":"Recurrent Pregnancy Loss in Women with Killer Cell Immunoglobulin-Like Receptor KIR2DS1 is Associated with an Increased HLA-C2 Allelic Frequency","volume":"75","author":"Dambaeva","year":"2015","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1600-0897.2009.00709.x","article-title":"Activating killer cell immunoglobulin-like receptor genes\u2019 association with recurrent miscarriage","volume":"62","author":"Vargas","year":"2009","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1093\/humrep\/dep047","article-title":"Influence of activating and inhibitory killer immunoglobulin-like receptors on predisposition to recurrent miscarriages","volume":"24","author":"Faridi","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/BF03195699","article-title":"Frequencies of killer immunoglobulin-like receptor genotypes influence susceptibility to spontaneous abortion","volume":"50","author":"Nowak","year":"2009","journal-title":"J. Appl. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jri.2010.11.001","article-title":"HLA-C C1C2 heterozygosity may protect women bearing the killer immunoglobulin-like receptor AA genotype from spontaneous abortion","volume":"88","author":"Nowak","year":"2011","journal-title":"J. Reprod. Immunol."},{"key":"ref_63","first-page":"477","article-title":"Influence of maternal killer-cell immunoglobulin-like receptors and parental HLA-C genotypes on predisposition to recurrent miscarriage","volume":"24","author":"Khosravifar","year":"2011","journal-title":"Iran J. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s10815-012-9811-1","article-title":"Evaluation of KIR genes in recurrent miscarriage","volume":"29","author":"Ozturk","year":"2012","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1093\/humrep\/deu251","article-title":"Maternal KIR haplotype influences live birth rate after double embryo transfer in IVF cycles in patients with recurrent miscarriages and implantation failure","volume":"29","author":"Alecsandru","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s00005-016-0389-7","article-title":"Possible Role of HLA-G, LILRB1 and KIR2DL4 Gene Polymorphisms in Spontaneous Miscarriage","volume":"64","author":"Nowak","year":"2016","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3389\/fimmu.2014.00389","article-title":"Regulatory T-Cells in Pregnancy: Historical Perspective, State of the Art, and Burning Questions","volume":"5","author":"Ruocco","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0167-5699(93)90235-D","article-title":"Bidirectional cytokine interactions in the maternal-fetal relationship: Is successful pregnancy a TH2 phenomenon?","volume":"14","author":"Wegmann","year":"1993","journal-title":"Immunol. Today"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jri.2009.12.003","article-title":"Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients","volume":"84","author":"Wang","year":"2010","journal-title":"J. Reprod. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1600-0897.2010.00812.x","article-title":"Accumulation of IL-17-Positive Cells in Decidua of Inevitable Abortion Cases","volume":"64","author":"Nakashima","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1007\/s10815-014-0294-0","article-title":"Association of IL-17A and IL-17 F gene polymorphisms with recurrent pregnancy loss in Iranian women","volume":"31","author":"Najafi","year":"2014","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1600-0897.2009.00771.x","article-title":"SHORT COMMUNICATION: Circulating and Decidual Th17 Cell Levels in Healthy Pregnancy","volume":"63","author":"Nakashima","year":"2009","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/humrep\/deu014","article-title":"Adoptive transfer of pregnancy-induced CD4+CD25+ regulatory T cells reverses the increase in abortion rate caused by interleukin 17 in the CBA\/JxBALB\/c mouse model","volume":"29","author":"Wang","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"759","DOI":"10.4049\/jimmunol.0803654","article-title":"Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17beta-estradiol","volume":"183","author":"Svensson","year":"2009","journal-title":"J. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","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":"ref_76","doi-asserted-by":"crossref","first-page":"157","DOI":"10.5582\/bst.2018.01012","article-title":"Distinct pattern of Th17\/Treg cells in pregnant women with a history of unexplained recurrent spontaneous abortion","volume":"12","author":"Qian","year":"2018","journal-title":"Biosci. Trends"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.earlhumdev.2012.08.003","article-title":"Assessment of sperm antigen specific T regulatory cells in women with recurrent miscarriage","volume":"89","author":"Liu","year":"2013","journal-title":"Early Hum. Dev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1177\/1933719116670517","article-title":"Treg\/Th17 Cell Imbalance and IL-6 Profile in Patients With Unexplained Recurrent Spontaneous Abortion","volume":"24","author":"Zhu","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1600-0897.2011.00992.x","article-title":"Low Circulating CD4+ CD25+ Foxp3+ T Regulatory Cell Levels Predict Miscarriage Risk in Newly Pregnant Women with a History of Failure","volume":"66","author":"Winger","year":"2011","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/S0002-9440(10)62302-4","article-title":"Abnormal T-Cell Reactivity against Paternal Antigens in Spontaneous Abortion: Adoptive Transfer of Pregnancy-Induced CD4+CD25+ T Regulatory Cells Prevents Fetal Rejection in a Murine Abortion Model","volume":"166","author":"Zenclussen","year":"2005","journal-title":"Am. J. Pathol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1355\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:28:16Z","timestamp":1760120896000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,8]]},"references-count":80,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12041355"],"URL":"https:\/\/doi.org\/10.3390\/jcm12041355","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,8]]}}}