{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:37:54Z","timestamp":1785584274094,"version":"3.56.0"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Estradiol (E2) and progesterone (P4) are steroid hormones important for the regulation of immune responses during pregnancy. Their increasing levels coincide with an improvement of T cell\u2010mediated diseases such as multiple sclerosis (MS). Although immune\u2010endocrine interactions are involved in this phenomenon, the relative contribution of hormones is not known. We here report a direct comparison of E2\u2010 and P4\u2010mediated effects on human CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, key cells in immune regulation. T cells were stimulated to obtain different activation levels and exposed to a broad range of hormone concentrations. Activation level was assessed by CD69\/CD25 expression by flow cytometry, and secreted proteins (\n                    <jats:italic>n<\/jats:italic>\n                    = 196) were measured in culture supernatants using proximity extension assay and electrochemiluminescence immunoassay. We found that in low activated cells, pregnancy\u2010relevant E2 concentrations increased activation and the secretion of several immune\u2010 and inflammation\u2010related proteins. P4, on the other hand, showed a biphasic pattern, where serum\u2010related concentrations upregulated activation and protein secretion while placenta\u2010relevant concentrations induced a prominent dampening irrespective of the initial activation level. Our results demonstrate the importance of P4 as a major hormone in the immune modulation of T cells during pregnancy and emphasize the need to further evaluate its potency in the treatment of diseases like MS.\n                  <\/jats:p>","DOI":"10.1002\/eji.202049144","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T07:45:21Z","timestamp":1625471121000},"page":"2430-2440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Differential effects of estradiol and progesterone on human T cell activation\n                    <i>in vitro<\/i>"],"prefix":"10.1002","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4373-5528","authenticated-orcid":false,"given":"Georgia","family":"Papapavlou","sequence":"first","affiliation":[{"name":"Division of Inflammation and Infection Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Hellberg","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics Department of Physics Chemistry and Biology Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Raffetseder","sequence":"additional","affiliation":[{"name":"Division of Inflammation and Infection Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Brynhildsen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Department of Obstetrics and Gynecology Faculty of Medicine \u00d6rebro University  \u00d6rebro Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics Department of Physics Chemistry and Biology Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Jenmalm","sequence":"additional","affiliation":[{"name":"Division of Inflammation and Infection Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Ernerudh","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Transfusion Medicine and Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3131"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623313482205"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2016.03.003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199807303390501"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker302"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.03051.x"},{"key":"e_1_2_10_8_1","first-page":"2227","article-title":"Cutting edge: estrogen drives expansion of the CD4+CD25+ regulatory T cell compartment","volume":"173","author":"Polanczyk M. J.","year":"2004","journal-title":"J Immunol Baltim Md 1950"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13395-019-0205-2"},{"key":"e_1_2_10_10_1","first-page":"159","article-title":"Low 17\u03b2\u2010estradiol Levels Are Better Inducers of Regulatory Conditioned T Cells In\u2010Vitro","volume":"14","author":"Fatemi R.","year":"2017","journal-title":"Iran J Immunol IJI"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00635"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0001"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.90"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01931"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-018-0726-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2014.04.004"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00322-1"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10301"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0426"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1617115114"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2008.10.002"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2012.02284.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445404"},{"key":"e_1_2_10_24_1","first-page":"1778","article-title":"Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells","volume":"187","author":"Lee J. H.","year":"2011","journal-title":"J Immunol Baltim Md 1950"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01293"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1213566"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112056"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2004.07.004"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3871"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20858"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20962"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062069"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.036"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_10_35_1","first-page":"3365","article-title":"Steroid hormone regulation of cytokine secretion by proteolipid protein\u2010specific CD4+ T cell clones isolated from multiple sclerosis patients and normal control subjects","volume":"161","author":"Correale J.","year":"1998","journal-title":"J Immunol Baltim Md 1950"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000148196"},{"key":"e_1_2_10_37_1","volume-title":"Endotext","author":"Reed B. G.","year":"2000"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-016-0937-5"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(84)90428-9"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00198"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-009-1125-x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01788"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2005.00633.x"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/15.3.713"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0378(89)90053-3"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/08830180215017"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmi008"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201970107"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095192"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202049144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.202049144","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202049144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:02:28Z","timestamp":1692950548000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.202049144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,26]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/eji.202049144"],"URL":"https:\/\/doi.org\/10.1002\/eji.202049144","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/EJI.202049144\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202049144\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202049144\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202049144\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202049144\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202049144\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202049144\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/EJI.202049144\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,26]]},"assertion":[{"value":"2020-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}