[beta]-Catenin Promotes the Differentiation of Epidermal Langerhans Dendritic Cells

• Published in: Journal of investigative dermatology Vol. 133; no. 5; p. 1250
• 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: London Elsevier Limited 01.05.2013
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2012.481

The epithelial signaling protein and transcriptional regulator [beta]-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 [beta]-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-[beta]1 (TGF-[beta]1). 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-[beta]1 induces [beta]-catenin in progenitor cells undergoing LC differentiation and that [beta]-catenin promotes LC differentiation. Vitamin D, another epidermal signal, enhanced TGF-[beta]1-mediated [beta]-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 [beta]-catenin on LC differentiation. Therefore, we here identified [beta]-catenin as a positive regulator of LC differentiation in response to TGF-[beta]1 and identified a functional interaction between [beta]-catenin and VDR in these cells.