title: Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin.
abstract: It remains largely unclear how antigen-presenting cells (APCs) encounter effector or memory T cells efficiently in the periphery. Here we used a mouse contact hypersensitivity (CHS) model to show that upon epicutaneous antigen challenge, dendritic cells (DCs) formed clusters with effector T cells in dermal perivascular areas to promote in situ proliferation and activation of skin T cells in a manner dependent on antigen and the integrin LFA-1. We found that DCs accumulated in perivascular areas and that DC clustering was abrogated by depletion of macrophages. Treatment with interleukin 1α (IL-1α) induced production of the chemokine CXCL2 by dermal macrophages, and DC clustering was suppressed by blockade of either the receptor for IL-1 (IL-1R) or the receptor for CXCL2 (CXCR2). Our findings suggest that the dermal leukocyte cluster is an essential structure for elicitating acquired cutaneous immunity.
authors.affiliation: 1] Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. [2] Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Natsuaki
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Gyohei
authors.initials: G
authors.lastname: Egawa
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamizo
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ono
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Hanakawa
authors.affiliation: Research Unit for Immunodynamics, RIKEN Research Center for Allergy and Immunology, Kanagawa, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kusuba
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otsuka
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kitoh
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Soken
authors.initials: S
authors.lastname: Tsuchiya
authors.affiliation: Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.affiliation: 1] Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Osaka, Japan. [2] Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.affiliation: Department of Microbiology, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: 1] Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan. [2] Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: 1] Laboratory for Cytokine Regulation, RIKEN center for Integrative Medical Science, Kanagawa, Japan. [2] Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Chiba, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.
authors.forename: Lai guan
authors.initials: Lg
authors.lastname: Ng
authors.affiliation: Department of Dermatology, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai School Medical Center, New York, New York,.
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes
authors.affiliation: Department of Dermatology, Icahn School of Medicine at Mount Sinai School Medical Center, New York, New York,.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
mesh_terms: D000818:Animals; D039521:CD11c Antigen / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000276:immunology; D053582:Interleukin-1alpha / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009504:Neutrophils / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors; D012867:Skin / Q000276:immunology* / Q000473:pathology
chemical_list: D039521:CD11c Antigen; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D053582:Interleukin-1alpha; D016169:Lymphocyte Function-Associated Antigen-1; D017472:Receptors, Interleukin-1; D023063:Receptors, Interleukin-8B