{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T22:56:27Z","timestamp":1771628187612,"version":"3.50.1"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Keratinocyte growth factor (KGF) has been proposed as a therapeutic adjuvant to enhance T cell immune reconstitution, particularly following stem cell transplantation. Here, we demonstrate that the long-term KGF-induced increase in thymic cellularity and thymocyte differentiation is preceded by a transient developmental block prior to the \u03b2-selection checkpoint, observed as early as day 2 following KGF treatment. This early block is characterized by an increased expansion of uncommitted thymocytes and is driven by KGF-induced alterations in both cortical and medullary thymic epithelial cells (TECs). KGF suppresses Wnt\/\u03b2-catenin signaling by downregulating distinct Wnt ligands in cTECs and mTECs, leading to reduced expression of FOXN1, a master regulator of TEC differentiation. Consequently, expression of\n                    <jats:italic>Foxn1<\/jats:italic>\n                    -dependent genes, including\n                    <jats:italic>Dll4<\/jats:italic>\n                    , a key Notch ligand required for early thymocyte development, is diminished. These findings reveal a novel mechanism of KGF action: an initial disruption of TEC-mediated signaling that transiently impairs early thymocyte differentiation, followed by enhanced proliferation and long-term thymic recovery.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1675823","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T06:30:05Z","timestamp":1763706605000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Disruption of Notch signaling by KGF induces a developmental pause in thymocytes"],"prefix":"10.3389","volume":"16","author":[{"given":"Ruifeng","family":"Teng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis 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