{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:52:42Z","timestamp":1768704762282,"version":"3.49.0"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81401683"],"award-info":[{"award-number":["81401683"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> excreted\u2010secreted antigens (ESA) cause spontaneous abortion or fetal teratogenesis during the pregnancy in mice, especially in the early stage. Those adverse pregnancy outcomes are due to the deficit in regulatory T cells (Tregs). Forkhead box P3 (Foxp3), a critical transcription factor, modulates Tregs differentiation and its function. Besides, phosphatidylinositol 3\u2010kinase\u2010protein kinase B\u2010mammalian target of rapamycin (PI3K\u2010AKT\u2010mTOR) signaling network is implicated in interfering with Foxp3 induction. We previously demonstrated that ESA diminished the number of Tregs and inhibited its function. And ESA suppressed Foxp3 expression via the attenuation of transforming growth factor \u03b2 RII\/Smad2\/Smad3\/Smad4 pathway. The current study aimed to investigate whether the PI3K\u2010AKT\u2010mTOR signaling network is involved in Foxp3 downregulation induced by ESA. We found that ESA upregulated PI3K, P\u2010AKT, mTOR, and P\u2010mTOR. Knockdown of PI3K cooperated with ESA to restore Foxp3 expression mediated by ESA. This suppressive role of ESA on Foxp3 expression was abrogated by AKT inhibitor. In addition, neutralization of Toll\u2010like receptor 4 could restore the expression of Foxp3, PI3K, and its downstream effectors induced by ESA. Collectively, the findings indicated that ESA inhibited Foxp3 expression via the upregulation of PI3K\u2010AKT\u2010mTOR signaling pathway.<\/jats:p>","DOI":"10.1002\/jcb.28884","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T03:52:02Z","timestamp":1557460322000},"page":"16044-16051","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>Toxoplasma gondii<\/i> excreted\u2010secreted antigens suppress Foxp3 via PI3K\u2010AKT\u2010mTOR signaling pathway"],"prefix":"10.1002","volume":"120","author":[{"given":"Jinling","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology School of Medicine Nantong University Nantong Jiangsu People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Medicine Nantong 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