title: CCR7-independent transport of skin antigens occurs in the dermis.
abstract: Under homeostatic conditions, skin DCs migrate to regional LNs transporting self-antigens (self-Ags). The transport of self-Ags is considered to be critical for maintaining peripheral tolerance. Although the chemokine receptor CCR7 potently induces the migration of skin DCs to regional LNs, Ccr7(-/-)  (Ccr7-KO) mice do not show skin auto-immune diseases. To resolve this inconsistency, we examined Ccr7-KO epidermis- or dermis-hyperpigmented transgenic (Tg) mice, in which the transport of skin self-Ags is traceable by melanin granules (MGs). Under CCR7-deficient conditions, the transport of epidermal MGs to regional LNs was impaired at 7 weeks of age. However, epidermal MGs could be transported when they had accumulated in the dermis. Ccr7-KO-dermis-pigmented Tg mice confirmed the presence of CCR7-independent transport from the dermis. Compared with WT-dermis-pigmented Tg mice, the amount of transported melanin and number of MG-laden CD11c(+)  cells were both approximately 40% of the WT levels, while the number of MG-laden CD205(+)  or CD207(+)  cells decreased to about 10% in skin regional LNs of Ccr7-KO-dermis-pigmented Tg mice. Cell sorting highlighted the involvement of CD11c(+)  cells in the CCR7-independent transport. Here, we show that CCR7-independent transport of skin self-Ags occurs in the dermis. This system might contribute to the continuous transport of self-Ags, and maintain peripheral tolerance.
authors.affiliation: Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Tottori, Japan. myoshi@med.tottori-u.ac.jp
authors.forename: Miya
authors.initials: M
authors.lastname: Yoshino
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okuyama
authors.forename: Akihiko
authors.initials: A
authors.lastname: Murata
authors.forename: Michio
authors.initials: M
authors.lastname: Tomura
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D001692:Biological Transport; D039521:CD11c Antigen / Q000032:analysis / Q000502:physiology; D020405:Dermis / Q000276:immunology*; D007108:Immune Tolerance; D008198:Lymph Nodes / Q000276:immunology; D008543:Melanins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054400:Receptors, CCR7 / Q000502:physiology*; D019089:Stem Cell Factor / Q000502:physiology
chemical_list: D001324:Autoantigens; D039521:CD11c Antigen; C515371:Ccr7 protein, mouse; D008543:Melanins; D054400:Receptors, CCR7; D019089:Stem Cell Factor