title: β-Catenin promotes the differentiation of epidermal Langerhans dendritic cells.
abstract: 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.
authors.affiliation: Institute of Immunology, Center of Pathophysiology, Infectiology, and Immunology, Medical University Vienna, Vienna, Austria.
authors.forename: Nighat
authors.initials: N
authors.lastname: Yasmin
authors.forename: Sabine
authors.initials: S
authors.lastname: Konradi
authors.forename: Gregor
authors.initials: G
authors.lastname: Eisenwort
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Schichl
authors.forename: Maria
authors.initials: M
authors.lastname: Seyerl
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauer
authors.forename: Johannes
authors.initials: J
authors.lastname: Stöckl
authors.forename: Herbert
authors.initials: H
authors.lastname: Strobl
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014807:Vitamin D / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D018167:Receptors, Calcitriol; D053773:Transforming Growth Factor beta1; D051176:beta Catenin; D014807:Vitamin D