title: CCR8 regulates contact hypersensitivity by restricting cutaneous dendritic cell migration to the draining lymph nodes.
abstract: Allergic contact dermatitis (ACD) is a typical occupational disease in industrialized countries. Although various cytokines and chemokines are suggested to be involved in the pathogenesis of ACD, the roles of these molecules remain to be elucidated. CC chemokine receptor 8 (CCR8) is one such molecule, of which expression is up-regulated in inflammatory sites of ACD patients. In this study, we found that Ccr8(-/-) mice developed severer contact hypersensitivity (CHS) responses to 2,4-dinitrofluorobenzene, a murine model of ACD, compared with wild-type mice. T cells from Ccr8(-/-) mice showed enhanced proliferative recall responses and Th1 and Th17 cell populations were expanded in these mice. However, CHS responses were similar between SCID mice adoptively transferred with Ccr8(-/-) and wild-type T cells, suggesting that CCR8 in T cells is not responsible for the exacerbation of CHS. Notably, skin-resident dendritic cells (DCs), such as Langerhans cells and dermal DCs, and inflammatory DCs were highly accumulated in lymph nodes (LNs) of Ccr8(-/-) mice after sensitization. Consistent with this, Ccr8(-/-) antigen-presenting cells readily migrated from the skin to the draining LNs after sensitization. These observations suggest that CCR8 negatively regulates migration of cutaneous DCs from the skin to the draining LNs in CHS by keeping these cells in the skin.
authors.affiliation: Center for Animal Disease Models, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan Medical Mycology Research Center, Chiba University, Inohana Chuo-ku, Chiba 260-8673, Japan.
authors.forename: Rikio
authors.initials: R
authors.lastname: Yabe
authors.affiliation: Center for Animal Disease Models, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Satoe
authors.initials: S
authors.lastname: Azechi
authors.affiliation: Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Byung-Il
authors.initials: BI
authors.lastname: Choi
authors.affiliation: Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.affiliation: Center for Animal Disease Models, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kubo
authors.affiliation: Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Harumichi
authors.initials: H
authors.lastname: Ishigame
authors.affiliation: Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kakuta
authors.affiliation: Center for Animal Disease Models, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo (IMSUT), Minato-ku, Tokyo 108-8639, Japan Medical Mycology Research Center, Chiba University, Inohana Chuo-ku, Chiba 260-8673, Japan Core Research for Evolutional and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan iwakura@rs.tus.ac.jp.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology*; D004139:Dinitrofluorobenzene; D007249:Inflammation / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D054401:Receptors, CCR8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: C489319:Ccr8 protein, mouse; D054401:Receptors, CCR8; D004139:Dinitrofluorobenzene
keywords: CCR8; Langerhans cells; contact hypersensitivity; dermal dendritic cells; migration