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SHR Neuro Cancer Cardio Lipid Metab Microb
Bauer, T; Richter-Eder, S; Yasmin, N; Jurkin, J; Köffel, R; Strobl, H.
Vitamin K supports TGF-β1 depended in vitro human Langerhans cell differentiation and function via Axl.
Front Immunol. 2025; 16:1509228
Doi: 10.3389/fimmu.2025.1509228
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- Leading authors Med Uni Graz
- Strobl Herbert
- Co-authors Med Uni Graz
- Köffel René
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- Abstract:
- INTRODUCTION: 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-β1 (TGF-β1) expressed by keratinocytes (KC) and LCs. We recently identified a crucial downstream effector of TGF-β1, 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. METHODS: We have now established that TGF-β1 dependent in vitro human LC generation from CD34+ progenitor cells can be enhanced by Axl over-expression. RESULTS: 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, in an Axl independent manner. DISCUSSION: Taken together, we provide evidence for the supportive role of vitamin K in regulating skin immunity.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Axl Receptor Tyrosine Kinase - administration & dosage
- Receptor Protein-Tyrosine Kinases - metabolism
- Langerhans Cells - metabolism, immunology
- Proto-Oncogene Proteins - metabolism
- Cell Differentiation - administration & dosage
- Vitamin K - pharmacology, metabolism
- Transforming Growth Factor beta1 - metabolism
- Cells, Cultured - administration & dosage
- Intercellular Signaling Peptides and Proteins - metabolism
- Protein S - metabolism
- Find related publications in this database (Keywords)
- dendritic cell
- Langerhans cell
- keratinocyte
- transforming growth factor
- receptor tyrosine kinase Axl