{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T01:06:22Z","timestamp":1783991182258,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds David et Alice Van Buuren"},{"name":"Belgian Kids\u2019 Fund"},{"name":"Fonds iris-Recherche"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Research has shown a sex-specific immune response, with males having a worse prognosis in acute inflammatory diseases. While these disparities were initially attributed to sex hormones, increasing evidence points to a predominant role for X-linked genetic factors. Toll-like receptors and several components of their signaling pathway are encoded on the X chromosome and may contribute to these differences. We investigated whether increase in circulating oestradiol influences TLR-dependent immune response. Sixteen women undergoing controlled ovarian hyperstimulation for in vitro fertilisation were studied. Whole blood collected before treatment, during stimulation and at ovulation triggering was stimulated with ligands targeting TLR2\/6, TLR1\/2, TLR4 and TLR7\/8. TLR2, TLR4 and CD99 expression, intracellular phosphorylated NF-\u03baB p65, ERK1\/2 and p38 MAPK, and cytokine production were assessed. Oestradiol levels increased markedly during treatment (48.1 to 1819.5 pg\/mL; p &lt; 0.001). Despite this rise, no or minimal impact on TLR2\/4 and CD99 expression, intracellular signalling or cytokine release was detected. Only IL-6 and IL-10 in response to TLR2\/6 stimulation increased significantly, with IL-6 positively associated with oestradiol variation. These findings indicate that oestradiol exerts a limited influence on TLR-dependent immune responses, supporting our view that sex-based immune differences are driven primarily by genetic rather than hormonal factors.<\/jats:p>","DOI":"10.3390\/cells15141257","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:55:21Z","timestamp":1783990521000},"page":"1257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Is Oestradiol a Key Player in the Sex Differences in Innate Immunity Through Toll-like Receptor Activation?"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8247-5613","authenticated-orcid":false,"given":"Alexandros","family":"Popotas","sequence":"first","affiliation":[{"name":"Laboratory of Pediatrics, Universit\u00e9 Libre de Bruxelles (ULB), 1020 Brussels, Belgium"},{"name":"Laboratory of Translational Research, Universit\u00e9 Libre de Bruxelles (ULB), 1020 Brussels, Belgium"},{"name":"Paediatric Emergency Department, Queen Fabiola Childrens University Hospital (H\u00f4pital Universitaire des Enfants Reine Fabiola)\u2014University Hospital of Brussels (H\u00f4pital Universitaire de Bruxelles), 1020 Brussels, Belgium"},{"name":"National Center for Pediatrics, Centre Hospitalier de Luxembourg, 1210 Luxembourg, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7236-0687","authenticated-orcid":false,"given":"Anne","family":"Delbaere","sequence":"additional","affiliation":[{"name":"Fertility Clinic, Department of Obstetrics and Gynecology, University Hospital of Brussels (H\u00f4pital Universitaire de Bruxelles\u2014H.U.B), CUB H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Casimir","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatrics, Universit\u00e9 Libre de Bruxelles (ULB), 1020 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Corazza","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Research, Universit\u00e9 Libre de Bruxelles (ULB), 1020 Brussels, Belgium"},{"name":"Laboratory of Immunology, Centre Hospitalier Universitaire (CHU) Brugmann, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6722-7267","authenticated-orcid":false,"given":"Viviane","family":"De Maertelaer","sequence":"additional","affiliation":[{"name":"Statistical Unit, Institut de Recherche Interdisciplinaire en Biologie Humaine et Mol\u00e9culaire (IRIBHM), Faculty of Medicine, Universit\u00e9 Libre de Bruxelles (ULB), 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7295-9361","authenticated-orcid":false,"given":"Nicolas","family":"Lef\u00e8vre","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatrics, Universit\u00e9 Libre de Bruxelles (ULB), 1020 Brussels, Belgium"},{"name":"Department of Pulmonology, Allergology and Cystic Fibrosis, Queen Fabiola Childrens University Hospital (H\u00f4pital Universitaire des Enfants Reine Fabiola)\u2014University Hospital of Brussels (H\u00f4pital Universitaire de Bruxelles), 1020 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex Differences in Immune Responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. 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[Ph.D. Thesis, Universit\u00e9 libre de Bruxelles]."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/14\/1257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T01:01:19Z","timestamp":1783990879000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/14\/1257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":32,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cells15141257"],"URL":"https:\/\/doi.org\/10.3390\/cells15141257","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]}}}