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Irritant-induced migration of Langerhans cells coincides with an IL-10-dependent switch to a macrophage-like phenotype.
MedLine Citation:
PMID:  21068755     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Langerhans cells (LCs) migrate after topical exposure of the skin to irritants, despite the supposed independence of irritant contact dermatitis from adaptive immunity. Whereas allergen-activated LCs are known to migrate to the draining lymph nodes (LNs), the fate of migrated LCs upon topical irritant exposure is unknown. Here, we identified a phenotypic switch of LCs after their migration into the dermis upon irritant exposure. With the aid of ex vivo intact human skin and epidermal sheets, we show that dermal fibroblasts are necessary for an IL-10-dependent postmigrational phenotypic switch of LCs into macrophage-like cells. Exposure of ex vivo skin to a panel of seven irritants resulted in a decrease in the number of CD1a(+) cells and an increase in CD14(+)/CD68(+) cells in the dermis. Neutralizing antibodies against IL-10 totally inhibited the phenotypic LC-to-macrophage transition, but did not influence the migration of CD1a(+) cells. Exposure of epidermal sheets to irritants resulted in a fibroblast-dependent LC-to-CD14(+)/CD68(+) switch coinciding with migration, which could be totally inhibited by neutralizing antibodies against either IL-10 or CCL2/CCL5 (two chemokines responsible for epidermal-to-dermal migration). We have thus identified an IL-10-dependent phenotypic switch of LCs into macrophage-like cells upon irritant exposure and emigration from the epidermis.
Authors:
Krista Ouwehand; Dinja Oosterhoff; Melanie Breetveld; Rik J Scheper; Tanja D de Gruijl; Susan Gibbs
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Publication Detail:
Type:  Journal Article     Date:  2010-11-11
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  131     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  418-25     Citation Subset:  IM    
Affiliation:
Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
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