title: Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis.
abstract: Intestinal immune homeostasis requires dynamic crosstalk between innate and adaptive immune cells. Dendritic cells (DCs) exist as multiple phenotypically and functionally distinct sub-populations within tissues, where they initiate immune responses and promote homeostasis. In the gut, there exists a minor DC subset defined as CD103(+)CD11b(-) that also expresses the chemokine receptor XCR1. In other tissues, XCR1(+) DCs cross-present antigen and contribute to immunity against viruses and cancer, however the roles of XCR1(+) DCs and XCR1 in the intestine are unknown. We showed that mice lacking XCR1(+) DCs are specifically deficient in intraepithelial and lamina propria (LP) T cell populations, with remaining T cells exhibiting an atypical phenotype and being prone to death, and are also more susceptible to chemically-induced colitis. Mice deficient in either XCR1 or its ligand, XCL1, similarly possess diminished intestinal T cell populations, and an accumulation of XCR1(+) DCs in the gut. Combined with transcriptome and surface marker expression analysis, these observations lead us to hypothesise that T cell-derived XCL1 facilitates intestinal XCR1(+) DC activation and migration, and that XCR1(+) DCs in turn provide support for T cell survival and function. Thus XCR1(+) DCs and the XCR1/XCL1 chemokine axis have previously-unappreciated roles in intestinal immune homeostasis.
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan.|Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.|Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.|Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Masanaka
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan.|Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.|Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hemmi
authors.affiliation: Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.|Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Okayama 700-8558, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yamazaki
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Okura
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan.|Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Sasaki
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan.|Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fukuda
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan.|Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Orimo
authors.affiliation: Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.|Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.|Department of Immunology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Hoshino
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 138648, Singapore.
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.affiliation: Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan.|Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.|Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Tsuneyasu
authors.initials: T
authors.lastname: Kaisho
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D019744:Chemokines, C / Q000172:deficiency / Q000378:metabolism*; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006706:Homeostasis; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D051379:Mice; D019707:Receptors, Chemokine / Q000172:deficiency / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D019744:Chemokines, C; D019707:Receptors, Chemokine; C551408:XC chemokine receptor 1, mouse; C486249:Xcl1 protein, mouse