{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:03:38Z","timestamp":1789542218876,"version":"build-2803163510"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001641"],"award-info":[{"award-number":["82001641"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anhui Province Natural Science Foundation of China","award":["2208085MH206"],"award-info":[{"award-number":["2208085MH206"]}]},{"name":"Anhui Province Natural Science Foundation of China","award":["2308085MH246"],"award-info":[{"award-number":["2308085MH246"]}]},{"name":"Anhui Provincial key laboratory of study on obstetric and Gynecologic diseases","award":["RDOGD-2024-08"],"award-info":[{"award-number":["RDOGD-2024-08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pregnancy represents a unique state of immune adaptation requiring precise regulation to maintain tolerance toward the semi-allogeneic fetus. Although natural killer (NK) cells and T cells play central roles in maternal-fetal immunity, gestational stage-specific expression patterns of immune checkpoint molecules Tim-3 and Lag-3, especially regarding their soluble forms, remain poorly characterized. This study comprehensively investigates T-cell immunoglobulin and mucin domain-3 (Tim-3) and Lymphocyte-activation gene 3 (Lag-3) in maternal immune regulation by integrating peripheral blood and decidual tissue analyses. In decidual NK (dNK) cells, single-cell RNA sequencing identified four distinct subsets (dNK1, dNK2, dNK3, and proliferating NKp cells) and revealed subset-specific immune checkpoint profiles: Tim-3 was highly expressed in dNK1 and dNK2, whereas Lag-3 showed consistently low expression. Patients with recurrent pregnancy loss (RPL) exhibited significantly reduced Tim-3 expression in key dNK subsets. Gene set enrichment analysis (GSEA) of Tim-3+ dNK cells identified significant enrichment in immune-related pathways, including chemokine signaling, cytokine-cytokine receptor interaction, and apoptosis. Peripheral analyses revealed dynamic gestational changes: Tim-3+ NK cells peaked early and declined, while Tim-3+ T cells gradually increased. Soluble Tim-3 levels negatively correlated with membrane-bound Tim-3 on NK cells, suggesting shedding-mediated regulation. Collectively, these findings underscore the spatial and temporal specificity of immune checkpoint regulation during pregnancy and indicate that dysregulated Tim-3 expression in both decidual and peripheral NK cells may contribute to impaired maternal-fetal immune tolerance in RPL.<\/jats:p>","DOI":"10.1093\/biolre\/ioag126","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:55:29Z","timestamp":1781870129000},"page":"789-801","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporal dynamics of natural killer cell immune checkpoints Tim-3 and Lag-3 in human pregnancy: an integrated peripheral and decidual compartment analysis"],"prefix":"10.1093","volume":"115","author":[{"given":"Daojing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui ,","place":["China"]},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine , Hefei, Anhui ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhong","family":"Tong","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui ,","place":["China"]},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine , Hefei, Anhui ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangting","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuojun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui ,","place":["China"]},{"name":"Core Unit of National Clinical Research Center for Laboratory Medicine , Hefei, Anhui ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, the First Affiliated Hospital of Anhui Medical University , Hefei, Anhui ,","place":["China"]},{"name":"Anhui Provincial Key Laboratory of Reproductive Disorders and Obstetrics and Gynaecology Diseases , Hefei, Anhui ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2842-2219","authenticated-orcid":false,"given":"Yanshi","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Reproduction and Genetics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"2026091602213223700_ref1","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1038\/s41577-025-01191-0","article-title":"Innate immune responses to 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