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Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis.
J Allergy Clin Immunol. 2001 Mar; 107(3):519-25.JA

Abstract

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.

Authors+Show Affiliations

Department of Dermatology, Ludwig-Maximilians-University, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11240954

Citation

Wollenberg, A, et al. "Topical Tacrolimus (FK506) Leads to Profound Phenotypic and Functional Alterations of Epidermal Antigen-presenting Dendritic Cells in Atopic Dermatitis." The Journal of Allergy and Clinical Immunology, vol. 107, no. 3, 2001, pp. 519-25.
Wollenberg A, Sharma S, von Bubnoff D, et al. Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis. J Allergy Clin Immunol. 2001;107(3):519-25.
Wollenberg, A., Sharma, S., von Bubnoff, D., Geiger, E., Haberstok, J., & Bieber, T. (2001). Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis. The Journal of Allergy and Clinical Immunology, 107(3), 519-25.
Wollenberg A, et al. Topical Tacrolimus (FK506) Leads to Profound Phenotypic and Functional Alterations of Epidermal Antigen-presenting Dendritic Cells in Atopic Dermatitis. J Allergy Clin Immunol. 2001;107(3):519-25. PubMed PMID: 11240954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topical tacrolimus (FK506) leads to profound phenotypic and functional alterations of epidermal antigen-presenting dendritic cells in atopic dermatitis. AU - Wollenberg,A, AU - Sharma,S, AU - von Bubnoff,D, AU - Geiger,E, AU - Haberstok,J, AU - Bieber,T, PY - 2001/3/10/pubmed PY - 2001/5/1/medline PY - 2001/3/10/entrez SP - 519 EP - 25 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 107 IS - 3 N2 - 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. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/11240954/Topical_tacrolimus__FK506__leads_to_profound_phenotypic_and_functional_alterations_of_epidermal_antigen_presenting_dendritic_cells_in_atopic_dermatitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(01)82464-7 DB - PRIME DP - Unbound Medicine ER -