Vitamin D receptor ablation alters skin architecture and homeostasis of dendritic epidermal T cells.
BACKGROUND
1alpha,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.


OBJECTIVE
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)(2)D(3) impaired LC maturation and T-cell stimulatory capacity from VDR(+/+) but not VDR(-/-) mice, demonstrating that LC are targets of vitamin D(3) and that interaction between vitamin D(3) 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.
Meindl
S
S
Novartis Institutes for BioMedical Research, Vienna, Austria.
Rot
A
A
Hoetzenecker
W
W
Kato
S
S
Cross
H S
HS
Elbe-Bürger
A
A
D000375:Aging / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D004817:Epidermis / Q000276:immunology / Q000473:pathology; D018859:Hair Follicle / Q000473:pathology; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018167:Receptors, Calcitriol / Q000172:deficiency / Q000502:physiology*; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
D018167:Receptors, Calcitriol; D003094:Collagen; D002117:Calcitriol