{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:37:15Z","timestamp":1792859835673,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"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","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Vertical transmission of\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    (\n                    <jats:italic>T. gondii<\/jats:italic>\n                    ) infection during gestation can result\u00a0in severe complications such as abortion, congenital malformation, fetal teratogenesis, etc. Immune inhibitory molecule Tim-3 was discovered to be expressed on some decidual immune cells and participates in the maintenance of maternal-fetal tolerance. Dysregulation of Tim-3 expression on decidual NK (dNK) cells was observed in several cases of pregnancy complications, whereas the role of Tim-3 on dNK cells during\n                    <jats:italic>T. gondii<\/jats:italic>\n                    infection remains unclear. In the present study,\n                    <jats:italic>T. gondii<\/jats:italic>\n                    infected Tim-3\n                    <jats:sup>-\/-<\/jats:sup>\n                    pregnant mice, and anti-Tim-3 neutralizing antibody treated and infected human dNK cells were successfully established to explore the role of Tim-3 in dysfunction of dNK cells during abnormal pregnancy. Our results illustrated that Tim-3\n                    <jats:sup>-\/-<\/jats:sup>\n                    pregnant mice displayed more worse pregnancy outcomes with\n                    <jats:italic>T. gondii<\/jats:italic>\n                    infection compared to infected WT pregnant mice. Also, it demonstrated that Tim-3 expression on dNK cells was significantly down-regulated following\n                    <jats:italic>T. gondii<\/jats:italic>\n                    infection. Data suggested a remarkable activation of dNK cells in Tim-3\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice and anti-Tim-3 neutralizing antibody treated and infected groups, with higher ratios of activating receptor NKG2D to inhibitory receptor NKG2A or KIR2DL4, IFN-\u03b3\/IL-10, and increased granule production compared with that of the infected group. Mechanism analysis proved that\n                    <jats:italic>T. gondii-<\/jats:italic>\n                    induced Tim-3 down-regulation significantly activated the phosphatidylinositol-3-kinase (PI3K)-AKT and JAK-STAT signaling pathway, by which the GranzymeB, Perforin, IFN-\u03b3, and IL-10 production were further up-regulated. Our research demonstrated that the decrease of Tim-3 on dNK cells caused by\n                    <jats:italic>T. gondii<\/jats:italic>\n                    infection further led to dNK cells function disorder, which finally contributed to the development of abnormal pregnancy outcomes.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2021.587150","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T07:32:38Z","timestamp":1614324758000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["The Role of Tim-3 on dNK Cells Dysfunction During Abnormal Pregnancy With Toxoplasma gondii Infection"],"prefix":"10.3389","volume":"11","author":[{"given":"Teng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianbing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.chom.2017.04.007","article-title":"Microbial vertical transmission during human pregnancy","volume":"21","author":"Arora","year":"2017","journal-title":"Cell Host Microbe"},{"key":"B2","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1111\/j.1600-0897.2011.00989.x","article-title":"Signal transducer and activator of transcription 3 (STAT3) and Suppressor of Cytokine Signaling (SOCS3) balance controls cytotoxicity and IL-10 expression in decidual-like natural killer cell line NK-92","volume":"66","author":"Braunschweig","year":"2011","journal-title":"Am. 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