title: Tracking and quantification of dendritic cell migration and antigen trafficking between the skin and lymph nodes.
abstract: Skin-derived dendritic cells (DCs) play a crucial role in the maintenance of immune homeostasis due to their role in antigen trafficking from the skin to the draining lymph nodes (dLNs). To quantify the spatiotemporal regulation of skin-derived DCs in vivo, we generated knock-in mice expressing the photoconvertible fluorescent protein KikGR. By exposing the skin or dLN of these mice to violet light, we were able to label and track the migration and turnover of endogenous skin-derived DCs. Langerhans cells and CD103(+)DCs, including Langerin(+)CD103(+)dermal DCs (DDCs), remained in the dLN for 4-4.5 days after migration from the skin, while CD103(-)DDCs persisted for only two days. Application of a skin irritant (chemical stress) induced a transient >10-fold increase in CD103(-)DDC migration from the skin to the dLN. Tape stripping (mechanical injury) induced a long-lasting four-fold increase in CD103(-)DDC migration to the dLN and accelerated the trafficking of exogenous protein antigens by these cells. Both stresses increased the turnover of CD103(-)DDCs within the dLN, causing these cells to die within one day of arrival. Therefore, CD103(-)DDCs act as sentinels against skin invasion that respond with increased cellular migration and antigen trafficking from the skin to the dLNs.
authors.affiliation: 1] Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan [2] Laboratory for Autoimmune Regulation, Research Center for Allergy and Immunology, RIKEN, 1-7-22 Suehiro-cho, Tsurumi, Yokohama City, Kanagawa 230-0045, Japan [3] Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3- 1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Tomura
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hata
authors.affiliation: 1] Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan [2].
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuoka
authors.affiliation: 1] Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3- 1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Francis H W
authors.initials: FH
authors.lastname: Shand
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan.
authors.forename: Ryoyo
authors.initials: R
authors.lastname: Ikebuchi
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3- 1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueha
authors.affiliation: Laboratory for Cell Function and Dynamics, Advanced Technology Development Center, Brain Science Institute, RIKEN.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Laboratory of Immunobiology, Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3- 1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.affiliation: 1] Laboratory for Cell Function and Dynamics, Advanced Technology Development Center, Brain Science Institute, RIKEN [2] Life Function and Dynamics, ERATO, JST, 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyawaki
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawara, Kyoto 606-8501, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.affiliation: 1] Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan [2].
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: 1] Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3- 1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2].
authors.forename: Osami
authors.initials: O
authors.lastname: Kanagawa
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D017453:Dermatitis, Irritant / Q000276:immunology / Q000473:pathology; D055879:Gene Knock-In Techniques; D039001:Integrin alpha Chains / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008027:Light; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D011506:Proteins / Q000235:genetics; D054400:Receptors, CCR7 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C515371:Ccr7 protein, mouse; D039001:Integrin alpha Chains; D011506:Proteins; C472408:ROSA22 protein, mouse; D054400:Receptors, CCR7; C091367:alpha E integrins
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