Original Article
Subject Category: Immunology/Infection
Journal of Investigative Dermatology (2006) 126, 1559–1573. doi:10.1038/sj.jid.5700328; published online 4 May 2006
A Chronic Contact Eczema Impedes Migration of Antigen-Presenting Cells in Alopecia Areata
Pooja Gupta1, Pia Freyschmidt-Paul2, Mario Vitacolonna1, Sabine Kiessling2, Susanne Hummel1, Dagmar Hildebrand1, Rachid Marhaba1 and Margot Zöller1,3
- 1Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg, Germany
- 2Department of Dermatology, University Hospital Marburg, Marburg, Germany
- 3Department of Applied Genetics, University of Karlsruhe, Karlsruhe, Germany
Correspondence: Dr Margot Zöller, Department of Tumor Progression and Immune Defense, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg D-69120, Germany. E-mail: m.zoeller@dkfz.de
Received 21 January 2006; Accepted 14 March 2005; Published online 4 May 2006.
Abstract
Long-lasting allergen treatment is the most efficient therapy in alopecia areata (AA). The underlying mechanism is unknown. We here asked whether treatment with a contact sensitizer influences leukocyte migration such that dendritic cell (DC) migration or the recruitment of activated T-cells towards the skin become hampered. Allergen treatment of AA mice was not accompanied by a decrease in skin-infiltrating leukocytes or draining lymph node cells (LNC). However, the distribution of leukocyte subsets was changed with a dominance of monocytes in the skin and a reduced percentage of DCs in draining nodes. Chemokine and chemokine receptor expression in skin and draining nodes was strikingly increased and LNC from untreated and allergen-treated AA mice showed high migratory activity in vitro and readily homed in draining nodes and skin after intravenous injection. However, FITC labelling of the skin and subcutaneous transfer of dye-labelled DC revealed that allergen treatment created a chemokine milieu severely hampering DC migration from the skin towards the draining node. An allergic eczema-induced reduction in DC migration and antigen transfer could well contribute to insufficient T-cell activation and the recovery of hair follicle in AA and possibly be of relevance for other skin-related autoimmune diseases.
Abbreviations:
AA, alopecia areata; AA/SADBE mice, SADBE-treated, AA-affected mice; APC, antigen-presenting cell; APCy, allophycocyanin; DC, dendritic cell; IFN, interferon; LNC, lymph node cell; M
, macrophage; OPN, osteopontin; SADBE, squaric acid dibutyl ester; SkIL, skin-infiltrating leukocytes; TNF, tumor necrosis factor
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