Ex-vivo Untersuchungen zur Arzneimittelwirkung topischer Tacrolimus (FK-506) Anwendung auf epidermale dendritische Zellen in läsionaler Haut bei Patienten mit atopischem Ekzem

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. CONCLUSION: Epidermal CD1a+ DCs may represent a
target for topical tacrolimus in the treatment of AD.