{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T18:46:21Z","timestamp":1786387581666,"version":"build-2736575974"},"posted":{"date-parts":[[2025,1,13]]},"group-title":"Immunology","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R00 HD098330"],"award-info":[{"award-number":["R00 HD098330"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Polycystic ovary syndrome (PMOS) is a complex reproductive disorder with clear genetic susceptibilities that impact the heterogeneous clinical presentation of symptoms and severity through unknown mechanisms. Chronic inflammation is linked to PMOS, but a clear cause-and-effect relationship between immune mediators and PMOS phenotypes has yet to be demonstrated. This study employed a comprehensive systems immunology approach, utilizing a letrozole-induced PMOS mouse model to identify changes in inflammatory factors associated with PMOS symptoms. By analyzing immune cells and secreted cytokines from 22 different mouse strains, we identified T cells and TNF-\u03b2 as associated with PMOS-like phenotypes, regardless of genetic background. We used a knockout of TCR\u03b1 to show that functional T cells are necessary for development of pathologically elevated luteinizing hormone (LH) in letrozole-treated female mice. In women with PMOS, we observed elevated TNF-\u03b2 transcripts in immune cells from women with PMOS. Finally, we demonstrate that TNF-\u03b2 increased Lhb mRNA in a female mouse gonadotrope-derived cell line, suggesting that TNF-\u03b2 may directly modulate gonadotrope gene expression and may contribute to elevated LH in PMOS-like conditions. These findings support a requirement for functional \u03b1\u03b2 T cells in LET-induced LH elevation in a PMOS-like mouse model and identify TNF-\u03b2 as a candidate immune mediator for further investigation.\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"631835v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Functional \u03b1\u03b2 T cells are linked to LET-induced LH elevation in a PMOS-like mouse model, uncovering candidate immune mechanisms for further study.<\/jats:p>\n                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