title: CCL5 and CCL20 mediate immigration of Langerhans cells into the epidermis of full thickness human skin equivalents.
abstract: Epidermal Langerhans cells (LC) play a key role in initiation and regulation of immune responses. Whereas LC migration out of the epidermis upon environmental assault is extensively studied, the mechanisms involved in the (re)population of the epidermis with LC are poorly understood. Here, we investigated the immigration of LC derived from the human MUTZ-3 cell line (MUTZ-LC) into the epidermis of a full thickness skin equivalent, comprising a fully differentiated epidermis on a fibroblast-populated dermis. MUTZ-LC were used to determine which epidermis-derived chemokines play a role in mediating LC trans-dermal migration into the epidermis. We found evidence for a role of keratinocyte-derived CCL5 and CCL20 in the chemo-attraction of MUTZ-LC. Neutralizing antibodies against CCL5 and CCL20 blocked LC migration towards keratinocytes. Secretion of these two chemokines was associated with incorporation of MUTZ-LC into the epidermis of full thickness skin equivalents. In conclusion, our findings suggest that epidermis derived CCL5 and CCL20 are pivotal mediators in recruitment of LC into 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: Sander W
authors.initials: SW
authors.lastname: Spiekstra
authors.forename: Taco
authors.initials: T
authors.lastname: Waaijman
authors.forename: Melanie
authors.initials: M
authors.lastname: Breetveld
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: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement; D054418:Chemokine CCL20 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020405:Dermis / Q000378:metabolism / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology; D007801:Langerhans Cells / Q000378:metabolism* / Q000502:physiology
chemical_list: D057134:Antibodies, Neutralizing; C108355:CCL20 protein, human; C483024:CCL5 protein, human; D054418:Chemokine CCL20; D018946:Chemokine CCL5