Tacrolimus and TGF-beta act synergistically on the generation of Langerhans cells.
BACKGROUND
The proportion of dendritic cell subpopulations in the skin is important for the severity of atopic dermatitis because topical treatment with tacrolimus leads to rapid depletion of inflammatory dendritic epidermal cells, whereas Langerhans cells (LCs) predominate in cured sites.


OBJECTIVE
The effects of tacrolimus and TGF-beta1 on LC differentiation and the idea of tacrolimus skewing the differentiation of epidermal precursors to LCs were evaluated.


METHODS
The presence of LC markers, MHC, and costimulatory molecules and stimulatory capacity toward T cells of monocyte-derived LCs were analyzed. Skin samples of patients with atopic dermatitis were assessed by means of immunofluorescence microscopy before and after tacrolimus treatment. TGF-beta production of skin cells was analyzed.


RESULTS
Tacrolimus and TGF-beta1 act synergistically on the generation of LCs and the expression of CD40, CD80, CD86, CD83, and MHC II; stabilize TGF-beta receptor II expression; and decrease the stimulatory capacity of LCs toward T cells. In vivo the number of epidermal LCs in tacrolimus-treated skin increased.


CONCLUSIONS
The synergism between TGF-beta1 and tacrolimus leads to the generation of LCs, reduced expression of costimulatory and MHC II molecules, and reduced stimulatory activity. Shifting the balance of the dendritic cell population to LCs might be of major importance for the therapeutic effect of tacrolimus.
Department of Dermatology and Allergology, University of Bonn, Bonn, Germany.
Bartlomiej
B
Kwiek
Wen-Ming
WM
Peng
Jean-Pierre
JP
Allam
Andrzej
A
Langner
Thomas
T
Bieber
Natalija
N
Novak
D000328:Adult; D002454:Cell Differentiation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology*; D004357:Drug Synergism; D004817:Epidermis / Q000276:immunology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000494:pharmacology*
D016207:Cytokines; D007166:Immunosuppressive Agents; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D016559:Tacrolimus