Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which antigen-presenting epidermal dendritic cells (DCs), ie, Langerhans cells and the so-called inflammatory dendritic epidermal cells (IDECs) expressing the high-affinity receptor for IgE (FcepsilonRI) may play a significant pathophysiologic role. Therapeutic efficacy of the immunosuppressive macrolide tacrolimus (FK506) in AD has been demonstrated in clinical trials, but little is known of its mode of action.


OBJECTIVE
The present study focused on the effects of topical tacrolimus treatment on epidermal CD1a+/FcepsilonRI+ DC populations in lesional AD.


METHODS
Immunohistological analysis, epidermal DC phenotyping, and functional studies were performed on skin biopsy specimens from treated and untreated lesional skin of 10 patients with AD participating in a clinical trial with tacrolimus.


RESULTS
Untreated lesional skin was characterized by a high proportion of CD1a+ cells, which was largely due to a high proportion of IDECs strongly expressing FcepsilonRI. Epidermal DCs isolated from untreated lesional skin exhibited high stimulatory activity toward autologous T cells, which was strongly reduced while clinical improvement was seen during application of tacrolimus. Concomitantly, a decreased FcepsilonRI expression was observed in both Langerhans cells and IDECs. Finally, topical tacrolimus led to a progressive decrease in the IDEC population within the pool of CD1a+ epidermal DCs and also to a decrease in their CD36 expression, which is indicative of lower local inflammation.


CONCLUSIONS
Epidermal CD1a+ DCs may represent a target for topical tacrolimus in the treatment of AD.
Department of Dermatology, Ludwig-Maximilians-University, Munich, Germany.
A
A
Wollenberg
S
S
Sharma
D
D
von Bubnoff
E
E
Geiger
J
J
Haberstok
T
T
Bieber
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000502:physiology*; D003713:Dendritic Cells / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D010641:Phenotype; D017455:Receptors, IgE / Q000096:biosynthesis; D012867:Skin / Q000473:pathology*; D016559:Tacrolimus / Q000008:administration & dosage* / Q000494:pharmacology
D017455:Receptors, IgE; D016559:Tacrolimus