{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:43:05Z","timestamp":1784893385846,"version":"3.55.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["PAT5056523, P27129, I4300B"],"award-info":[{"award-number":["PAT5056523, P27129, I4300B"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"Introduction<\/jats:title>On the outermost edge of the body a dense network of dendritic cells (DCs), the so-called Langerhans cells (LCs), represents the first immune barrier. The establishment and maintenance of this epidermal network is dependent on the cytokine transforming growth factor-\u03b21 (TGF-\u03b21) expressed by keratinocytes (KC) and LCs. We recently identified a crucial downstream effector of TGF-\u03b21, the receptor tyrosine kinase Axl. Axl belongs to the TAM receptor family, which also includes Tyro3 and Mer, and is activated through the vitamin K-dependent ligands Gas6 and Protein S.<\/jats:p><\/jats:sec>Methods<\/jats:title>We have now established that TGF-\u03b21 dependent in vitro<\/jats:italic> human LC generation from CD34+<\/jats:sup> progenitor cells can be enhanced by Axl over-expression.<\/jats:p><\/jats:sec>Results<\/jats:title>Additionally, we supplemented vitamin K into serum-free human LC generation cultures in order to activate the endogenous ligands Gas6 and Protein S. Vitamin K exhibited supportive effects on LC differentiation and LC-associated gene expression. The vitamin K antagonist warfarin on the other hand, hindered efficient LC differentiation. Blocking antibodies against Axl abrogated the positive effect of vitamin K on LC differentiation. Lastly, vitamin K downregulated the immune activation marker CD86 during LC differentiation and blocked the upregulation of CD86 during LC activation in vitro<\/jats:italic>, in an Axl independent manner.<\/jats:p><\/jats:sec>Discussion<\/jats:title>Taken together, we provide evidence for the supportive role of vitamin K in regulating skin immunity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1509228","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T06:52:24Z","timestamp":1739861544000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Vitamin K supports TGF-\u03b21 depended in vitro human Langerhans cell differentiation and function via 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