{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:03:12Z","timestamp":1787166192186,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011329","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000}}],"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021QH089"],"award-info":[{"award-number":["ZR2021QH089"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871680"],"award-info":[{"award-number":["81871680"]}],"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","award":["81672049"],"award-info":[{"award-number":["81672049"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012620","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ts201712066"],"award-info":[{"award-number":["ts201712066"]}],"id":[{"id":"10.13039\/100012620","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Myeloid-derived suppressor cells (MDSCs) play a key role in maintaining maternal-fetal tolerance for a successful pregnancy, but the role of MDSCs in abnormal pregnancy caused by\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    infection is unknown. Herein, we revealed a distinct mechanism by which T-cell immunoglobulin domain and mucin domain containing protein-3 (Tim-3), an immune checkpoint receptor that balances maternal-fetal tolerance during pregnancy, contributes to the immunosuppressive function of MDSCs during\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection. The expression of Tim-3 in decidual MDSCs was significantly downregulated following\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection. The proportion of monocytic MDSCs population, the inhibitory effect of MDSCs on T-cell proliferation, the levels of STAT3 phosphorylation, and the expression of functional molecules (Arg-1 and IL-10) in MDSCs were all decreased in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii-<\/jats:italic>\n                    infected pregnant Tim-3 gene knockout (Tim-3KO) mice compared with infected pregnant WT mice. After treatment with Tim-3-neutralizing Ab\n                    <jats:italic>in vitro<\/jats:italic>\n                    , the expression levels of Arg-1, IL-10, C\/EBP\u03b2, and p-STAT3 were decreased, the interaction between Fyn and Tim-3 or between Fyn and STAT3 was weakened, and the binding ability of C\/EBP\u03b2 to the promoters of\n                    <jats:italic>ARG1<\/jats:italic>\n                    and\n                    <jats:italic>IL10<\/jats:italic>\n                    was decreased in human decidual MDSCs with\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection, while opposite results were observed following treatment with galectin-9 (a ligand for Tim-3). Inhibitors of Fyn and STAT3 also downregulated the expression of Arg-1 and IL-10 in decidual MDSCs and exacerbated adverse pregnancy outcomes caused by\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection in mice. Therefore, our studies discovered that the decrease of Tim-3 after\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection could downregulate the functional molecules of Arg-1 and IL-10 expression in decidual MDSCs through the Fyn-STAT3-C\/EBP\u03b2 signaling pathway and weaken their immunosuppressive function, which eventually contribute to the development of adverse pregnancy outcomes.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011329","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T13:44:04Z","timestamp":1681479844000},"page":"e1011329","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Tim-3 regulates the immunosuppressive function of decidual MDSCs via the Fyn-STAT3-C\/EBP\u03b2 pathway during Toxoplasma gondii infection"],"prefix":"10.1371","volume":"19","author":[{"given":"Houbao","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuantao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianbing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhidan","family":"Li","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3584-5639","authenticated-orcid":true,"given":"Xuemei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,14]]},"reference":[{"key":"ppat.1011329.ref001","doi-asserted-by":"crossref","first-page":"587150","DOI":"10.3389\/fcimb.2021.587150","article-title":"The 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Zhang","year":"2019","journal-title":"Inflammation"},{"issue":"4","key":"ppat.1011329.ref004","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.pt.2020.10.013","article-title":"Toxoplasma Effectors that Affect Pregnancy Outcome","volume":"37","author":"D Arranz-Sol\u00eds","year":"2021","journal-title":"Trends in parasitology"},{"issue":"11","key":"ppat.1011329.ref005","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1002\/eji.201040895","article-title":"The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity","volume":"40","author":"JI Youn","year":"2010","journal-title":"European journal of immunology"},{"issue":"7","key":"ppat.1011329.ref006","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.intimp.2011.01.003","article-title":"Myeloid derived suppressor cells in human diseases","volume":"11","author":"TF Greten","year":"2011","journal-title":"International 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