title: Skin irritants and contact sensitizers induce Langerhans cell migration and maturation at irritant concentration.
abstract: Skin irritants and contact allergens reduce the number of Langerhans cells (LCs). It has been assumed that this reduction is due their migration to the draining lymph node (LN) for initiating immune sensitization in a host. Skin irritation, however, as opposed to contact allergy is not considered to be an immunological disease. Nevertheless, skin irritants are also known for their adjuvant-like effects on contact allergy, resulting in skin hypersensitivity reactions like toxic dermatitis. The human organotypic skin explant culture (hOSEC) model is used to study the characteristics of chemical-induced migration of CD1a(+) LCs out of the epidermis in relation to irritancy or toxicity. We analysed cells emigrating out of hOSEC for CD1a(+) LCs, CD83(+) mature dendritic cells (DCs) and CCR7(+) LN homing cells. After exposure to a toxic concentration of a non-immunogenic irritant, an increase of CD1a(+)CD83(+) LCs was found in the culture medium. A non-toxic concentration of an sensitizer induced an increase of CD1a(+) cells. About 50% of skin emigrating CD1a(+) LCs were CD83(-) (immature) but all were CCR7(+). Skin irritation by both non-allergenic and allergenic compounds induces LC migration and maturation. In contrast, only allergenic compounds induced LC migration with partial maturation at subtoxic concentration. This effectively demonstrates that irritation is physiologically needed stimuli for inducing LC maturation.
authors.affiliation: Department of Pathobiology, Utrecht University, Utrecht, The Netherlands.
authors.forename: John J L
authors.initials: JJ
authors.lastname: Jacobs
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Lehé
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Graham R
authors.initials: GR
authors.lastname: Elliott
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Das
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003877:Dermatitis, Contact / Q000209:etiology / Q000473:pathology; D009783:Dermatitis, Occupational / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D007509:Irritants / Q000008:administration & dosage / Q000633:toxicity*; D007801:Langerhans Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000473:pathology; D023422:Skin Irritancy Tests; D046509:Tissue Culture Techniques
chemical_list: D000485:Allergens; D007509:Irritants