title: Epidermis-to-dermis migration of immature Langerhans cells upon topical irritant exposure is dependent on CCL2 and CCL5.
abstract: Skin irritation is generally not considered to be an immunological event; however, alterations in the density of Langerhans cells (LC) in the epidermis do occur, which is indicative of LC migration. In this study, we investigated the migration of LC out of the epidermis after skin exposure to contact irritants and identified the chemokines involved. With the aid of ex vivo-intact human skin and epidermal sheets we show that dermal fibroblasts play a role in mediating LC migration towards the dermis. Exposure of ex vivo-intact human skin to a panel of seven irritants (SDS, salicylic acid, phenol, isopropanol, DMSO, TritonX, or benzalkonium chloride) resulted in decreased numbers of CD1a(+) cells in the epidermis and the accumulation of CD1a(+) cells in the dermis. In contrast to allergen exposure, neutralizing antibodies to either CXCL12 or CCL19/CCL21 did not inhibit LC migration out of the epidermis. Exposure of epidermal sheets to the prototypical irritant SDS resulted in a TNF-alpha-dependent LC migration towards dermal fibroblasts. This was a result of CCL2/MCP-1 and CCL5/RANTES chemokine secretion by fibroblasts: injection of CCL2- and CCL5-neutralizing antibodies into intact human skin totally inhibited LC migration into the dermis. We have thus identified a novel role for TNF-alpha-inducible dermis-derived CCL2 and CCL5 in initiating migration of irritant-exposed human LC out of the epidermis.
authors.affiliation: Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Krista
authors.initials: K
authors.lastname: Ouwehand
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.forename: Susan
authors.initials: S
authors.lastname: Gibbs
mesh_terms: D019138:Antibodies, Blocking / Q000008:administration & dosage; D018949:Antigens, CD1 / Q000096:biosynthesis; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism*; D020405:Dermis / Q000187:drug effects / Q000473:pathology; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007271:Injections, Intradermal; D007509:Irritants / Q000008:administration & dosage*; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D018949:Antigens, CD1; C419393:CD1a antigen; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D007509:Irritants; D014409:Tumor Necrosis Factor-alpha