Vitamin D receptor ablation alters skin architecture and homeostasis of dendritic epidermal T cells

Research output: Contribution to journalArticle

Authors

  • S Meindl
  • W Hoetzenecker
  • S Kato
  • HS Cross
  • A Elbe-Burger

Colleges, School and Institutes

Abstract

Background 1 alpha,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], the active metabolite of vitamin D, exerts its activities by binding to the vitamin D receptor (VDR) with subsequent function as a transcription factor. Targeted ablation of the VDR in mice results in rickets and alopecia. Objectives To study the consequences of VDR deficiency for skin physiology, and to investigate the mechanisms of the immunosuppressive effect of 1,25(OH)(2)D-3 on LC. Methods We studied the structural, phenotypic and functional properties of skin and individual skin leucocyte populations in VDR-/- mice. Results The lack of VDR induced a wide spectrum of pathologies including dermal deposition of collagen, enlargement of sebaceous glands, dilation of the hair follicles, development of epidermal cysts, increased numbers of dendritic epidermal T cells (DETC) and hyperkeratosis. Ageing aggravated these changes. Intriguingly, Langerhans cells (LC) were indistinguishable in distribution, morphology and number compared with controls. In vitro, LC underwent a maturation/migration process similar to LC from control mice. Pretreatment of epidermal cells or LC-enriched epidermal cell suspensions with 1,25(OH)2D3 impaired LC maturation and T-cell stimulatory capacity from VDR+/+ but not VDR-/- mice, demonstrating that LC are targets of vitamin D3 and that interaction between vitamin D3 and LC results in a suppression of LC activity. Conclusions Our data imply that VDR expression controls dermal collagen production, hair development and growth, proliferation of sebaceous glands and the homeostasis of DETC. Surprisingly, VDR deficiency does not influence LC phenotype and function.

Details

Original languageEnglish
Pages (from-to)231-241
Number of pages11
JournalBritish Journal of Dermatology
Volume152
Issue number2
Publication statusPublished - 1 Feb 2005

Keywords

  • Langerhans cells, dendritic epidermal T cells, mouse, vitamin D receptor, skin