{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T05:52:26Z","timestamp":1773640346035,"version":"3.50.1"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Pregnancy causes abrupt thymic atrophy. This atrophy is characterized by a severe decrease in the number of all thymocyte subsets and qualitative (but not quantitative) changes in thymic epithelial cells (TECs). Pregnancy-related thymic involution is triggered by progesterone-induced functional changes affecting mainly cortical TECs (cTECs). Remarkably, this severe involution is rapidly corrected following parturition. We postulated that understanding the mechanisms of pregnancy-related thymic changes could provide novel insights into signaling pathways regulating TEC function. When we analyzed genes whose expression in TECs was modified during late pregnancy, we found a strong enrichment in genes bearing KLF4 transcription factor binding motifs. We, therefore, engineered a <jats:italic>Psmb11-iCre : Klf4<jats:sup>lox\/lox<\/jats:sup><\/jats:italic> mouse model to study the impact of TEC-specific <jats:italic>Klf4<\/jats:italic> deletion in steady-state conditions and during late pregnancy. Under steady-state conditions, <jats:italic>Klf4<\/jats:italic> deletion had a minimal effect on TEC subsets and did not affect thymic architecture. However, pregnancy-induced thymic involution was much more pronounced in pregnant females lacking <jats:italic>Klf4<\/jats:italic> expression in TECs. These mice displayed a substantial ablation of TECs with a more pronounced loss of thymocytes. Transcriptomic and phenotypic analyses of <jats:italic>Klf4<\/jats:italic><jats:sup>-\/-<\/jats:sup> TECs revealed that <jats:italic>Klf4<\/jats:italic> maintains cTEC numbers by supporting cell survival and preventing epithelial-to-mesenchymal plasticity during late pregnancy. We conclude that <jats:italic>Klf4<\/jats:italic> is essential for preserving TEC\u2019s integrity and mitigating thymic involution during late pregnancy.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1016378","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T05:24:20Z","timestamp":1682573060000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Klf4 protects thymus integrity during late pregnancy"],"prefix":"10.3389","volume":"14","author":[{"given":"Lucyle","family":"Depo\u00ebrs","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maude","family":"Dumont-Lagac\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent 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