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Vitamin K supports TGF-β1 depended in vitro human Langerhans cell differentiation and function via Axl
Thomas Bauer1,2, Susanne Richter-Eder3, Nighat Yasmin3
1Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
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.
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