PMID- 27005831 OWN - NLM STAT- MEDLINE DCOM- 20170125 LR - 20221109 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Mar 23 TI - Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis. PG - 23505 LID - 10.1038/srep23505 [doi] LID - 23505 AB - 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. FAU - Ohta, Tomokazu AU - Ohta T AD - Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. AD - Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan. AD - Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. FAU - Sugiyama, Masanaka AU - Sugiyama M AD - Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. AD - Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. AD - Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. AD - Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. FAU - Hemmi, Hiroaki AU - Hemmi H AD - Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. AD - Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan. AD - Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. AD - Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. FAU - Yamazaki, Chihiro AU - Yamazaki C AD - Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. AD - Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Okayama 700-8558, Japan. FAU - Okura, Soichiro AU - Okura S AD - Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. AD - Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan. FAU - Sasaki, Izumi AU - Sasaki I AD - Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. AD - Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan. AD - Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. FAU - Fukuda, Yuri AU - Fukuda Y AD - Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. AD - Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan. AD - Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. FAU - Orimo, Takashi AU - Orimo T AD - Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. AD - Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan. AD - Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. FAU - Ishii, Ken J AU - Ishii KJ AD - Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan. AD - Laboratory of Vaccine Science, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. FAU - Hoshino, Katsuaki AU - Hoshino K AD - Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. AD - Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. AD - Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. AD - Department of Immunology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan. FAU - Ginhoux, Florent AU - Ginhoux F AD - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 138648, Singapore. FAU - Kaisho, Tsuneyasu AU - Kaisho T AD - Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. AD - Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Wakayama 641-8509, Japan. AD - Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. AD - Laboratory for Host Defence, RIKEN Center for Integrative Medical Science (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160323 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Chemokines, C) RN - 0 (Receptors, Chemokine) RN - 0 (XC chemokine receptor 1, mouse) RN - 0 (Xcl1 protein, mouse) SB - IM MH - Animals MH - Cell Movement MH - Cell Proliferation MH - Cell Survival MH - Cells, Cultured MH - Chemokines, C/deficiency/*metabolism MH - Cross-Priming MH - Dendritic Cells/immunology/*physiology MH - Gene Expression Profiling/methods MH - Gene Expression Regulation MH - Homeostasis MH - Intestines/cytology/*immunology MH - Mice MH - Receptors, Chemokine/deficiency/*metabolism MH - T-Lymphocytes/*cytology/immunology PMC - PMC4804307 EDAT- 2016/03/24 06:00 MHDA- 2017/01/26 06:00 PMCR- 2016/03/23 CRDT- 2016/03/24 06:00 PHST- 2015/12/08 00:00 [received] PHST- 2016/03/08 00:00 [accepted] PHST- 2016/03/24 06:00 [entrez] PHST- 2016/03/24 06:00 [pubmed] PHST- 2017/01/26 06:00 [medline] PHST- 2016/03/23 00:00 [pmc-release] AID - srep23505 [pii] AID - 10.1038/srep23505 [doi] PST - epublish SO - Sci Rep. 2016 Mar 23;6:23505. doi: 10.1038/srep23505.