β-Catenin Promotes the Differentiation of Epidermal Langerhans Dendritic Cells

• Published in: Journal of investigative dermatology Vol. 133; no. 5; pp. 1250 - 1259
• Main Authors: Yasmin, Nighat, Konradi, Sabine, Eisenwort, Gregor, Schichl, Yvonne M., Seyerl, Maria, Bauer, Thomas, Stöckl, Johannes, Strobl, Herbert
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2013
• Subjects: beta Catenin - metabolism; Cadherins - metabolism; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cells, Cultured; Epidermal Cells; Epidermis - drug effects; Epidermis - metabolism; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Humans; In Vitro Techniques; Langerhans Cells - cytology; Langerhans Cells - drug effects; Langerhans Cells - metabolism; Receptors, Calcitriol - metabolism; Signal Transduction - physiology; Transforming Growth Factor beta1 - pharmacology; Vitamin D - pharmacology
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2012.481

The epithelial signaling protein and transcriptional regulator β-catenin has recently been implicated in hematopoietic dendritic cell (DC) differentiation as well as in DC-mediated tolerance. We here observed that epidermal Langerhans cells (LCs) but not interstitial/dermal DCs express detectable β-catenin. LCs are unique among the DC family members in that LC networks critically depend on epithelial adhesion molecules as well as on the cytokine transforming growth factor-β1 (TGF-β1). However, despite the important functions of LCs in the immune system, the molecular mechanisms governing LC differentiation and maintenance remain poorly defined. We found that TGF-β1 induces β-catenin in progenitor cells undergoing LC differentiation and that β-catenin promotes LC differentiation. Vitamin D, another epidermal signal, enhanced TGF-β1-mediated β-catenin induction and promoted the expression of multiple epithelial genes by LCs. Moreover, full-length vitamin D receptor (VDR) promoted, whereas a truncated VDR diminished, the positive effects of ectopic β-catenin on LC differentiation. Therefore, we here identified β-catenin as a positive regulator of LC differentiation in response to TGF-β1 and identified a functional interaction between β-catenin and VDR in these cells.