Irritant-induced migration of Langerhans cells coincides with an IL-10-dependent switch to a macrophage-like phenotype.
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.
Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
Krista
K
Ouwehand
Dinja
D
Oosterhoff
Melanie
M
Breetveld
Rik J
RJ
Scheper
Tanja D
TD
de Gruijl
Susan
S
Gibbs
D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001706:Biopsy; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000378:metabolism / Q000473:pathology; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D007509:Irritants / Q000494:pharmacology*; D007801:Langerhans Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010636:Phenols / Q000494:pharmacology; D010641:Phenotype; D020156:Salicylic Acid / Q000494:pharmacology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004121:Dimethyl Sulfoxide; D016753:Interleukin-10; D007509:Irritants; D018950:Lipopolysaccharide Receptors; D010636:Phenols; D020156:Salicylic Acid; C067980:CD68 antigen, human; D000097382:CD68 Molecule