{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:11:33Z","timestamp":1788786693837,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004166","name":"Medical University of Warsaw, Poland","doi-asserted-by":"publisher","award":["1MG\/M\/MB1\/N\/20"],"award-info":[{"award-number":["1MG\/M\/MB1\/N\/20"]}],"id":[{"id":"10.13039\/501100004166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004166","name":"department statutory","doi-asserted-by":"publisher","award":["1MG\/N\/2019"],"award-info":[{"award-number":["1MG\/N\/2019"]}],"id":[{"id":"10.13039\/501100004166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recurrent pregnancy loss (RPL) is defined as the loss of two or more pregnancies before the 22nd gestational week and affects 10\u201315% of clinical pregnancies. Despite extensive diagnostics, over 50% of RPL cases remain unexplained, suggesting an important role for immunological mechanisms. Sex hormones (SH) are key regulators of immune responses during pregnancy; however, their influence on immune checkpoint proteins (ICPs) is poorly understood. This study evaluated the effects of progesterone, \u03b2-estradiol, and dihydrotestosterone (DHT) on ICP expression on immune cells, including Treg, NK, NKT, TC, Th, and T cells, collected from pregnant women and patients with unexplained RPL (uRPL). Peripheral blood mononuclear cells from 20 pregnant women and 20 uRPL patients were cultured for 48 h with SH. The expression of the first generation of ICPs\u2014PD-1 and TIM-3\u2014and the second\u2014LAG-3, TIGIT, and VISTA\u2014on T, NK, and NKT cells was analyzed by the flow cytometry method. In pregnant women, SH exerted modest effects, with DHT increasing VISTA and LAG-3 expression, while progesterone and estradiol mainly upregulated LAG-3 and TIM-3 on cytotoxic cells. In contrast, uRPL immune cells showed pronounced SH sensitivity, characterized by increased TIM-3 and VISTA expression and reduced TIGIT expression, particularly after DHT stimulation. In conclusion, SH modulates ICP expression in a cell-specific manner, with stronger effects observed in uRPL patients\u2019 lymphocytes. These findings highlight a potential role for hormonal and ICP-targeted strategies in RPL management.<\/jats:p>","DOI":"10.3390\/ijms27031265","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:35:42Z","timestamp":1769513742000},"page":"1265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sex Hormones-Mediated Modulation of Immune Checkpoints in Pregnancy and Recurrent Pregnancy Loss"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7539-5743","authenticated-orcid":false,"given":"Micha\u0142","family":"Zych","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology Medical, University of Warsaw, 02-006 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Roszczyk","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Medical, University of Warsaw, 02-006 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2885-7263","authenticated-orcid":false,"given":"Marzenna","family":"Zakrzewska","sequence":"additional","affiliation":[{"name":"Department of Logic and Cognitive Science, Faculty of Psychology, Adam Mickiewicz University, 61-712 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7957-2372","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Zago\u017cd\u017con","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Genetic Therapies, Medical University of Warsaw, 02-091 Warsaw, Poland"},{"name":"Department of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0160-3009","authenticated-orcid":false,"given":"Leszek","family":"P\u0105czek","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Medical, University of Warsaw, 02-006 Warsaw, Poland"},{"name":"Department of Bioinformatics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-091 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8557-4091","authenticated-orcid":false,"given":"Filip Andrzej","family":"D\u0105browski","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Gynecological Oncology, Medical Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-7236","authenticated-orcid":false,"given":"Monika Joanna","family":"Kniotek","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Medical, University of Warsaw, 02-006 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1097\/CM9.0000000000003114","article-title":"Role of maternal-fetal immune tolerance in the establishment and maintenance of pregnancy","volume":"137","author":"Wang","year":"2024","journal-title":"Chin. 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