PMID- 26755602 OWN - NLM STAT- MEDLINE DCOM- 20160617 LR - 20181113 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 113 IP - 4 DP - 2016 Jan 26 TI - Imaging of the cross-presenting dendritic cell subsets in the skin-draining lymph node. PG - 1044-9 LID - 10.1073/pnas.1513607113 [doi] AB - Dendritic cells (DCs) are antigen-presenting cells specialized for activating T cells to elicit effector T-cell functions. Cross-presenting DCs are a DC subset capable of presenting antigens to CD8(+) T cells and play critical roles in cytotoxic T-cell-mediated immune responses to microorganisms and cancer. Although their importance is known, the spatiotemporal dynamics of cross-presenting DCs in vivo are incompletely understood. Here, we study the T-cell zone in skin-draining lymph nodes (SDLNs) and find it is compartmentalized into regions for CD8(+) T-cell activation by cross-presenting DCs that express the chemokine (C motif) receptor 1 gene, Xcr1 and for CD4(+) T-cell activation by CD11b(+) DCs. Xcr1-expressing DCs in the SDLNs are composed of two different populations: migratory (CD103(hi)) DCs, which immigrate from the skin, and resident (CD8alpha(hi)) DCs, which develop in the nodes. To characterize the dynamic interactions of these distinct DC populations with CD8(+) T cells during their activation in vivo, we developed a photoconvertible reporter mouse strain, which permits us to distinctively visualize the migratory and resident subsets of Xcr1-expressing DCs. After leaving the skin, migratory DCs infiltrated to the deep T-cell zone of the SDLNs over 3 d, which corresponded to their half-life in the SDLNs. Intravital two-photon imaging showed that after soluble antigen immunization, the newly arriving migratory DCs more efficiently form sustained conjugates with antigen-specific CD8(+) T cells than other Xcr1-expressing DCs in the SDLNs. These results offer in vivo evidence for differential contributions of migratory and resident cross-presenting DCs to CD8(+) T-cell activation. FAU - Kitano, Masahiro AU - Kitano M AD - Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Translational Imaging Center, University of Southern California, Los Angeles, CA 90089; FAU - Yamazaki, Chihiro AU - Yamazaki C AD - Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; Department of Allergy and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Department of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Okayama 700-8558, Japan; FAU - Takumi, Akiko AU - Takumi A AD - Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; FAU - Ikeno, Takashi AU - Ikeno T AD - Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Laboratory of Lymphocyte Differentiation, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan; FAU - Hemmi, Hiroaki AU - Hemmi H AD - Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; 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; FAU - Takahashi, Noriko AU - Takahashi N AD - Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; FAU - Shimizu, Kanako AU - Shimizu K AD - Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; FAU - Fraser, Scott E AU - Fraser SE AD - Translational Imaging Center, University of Southern California, Los Angeles, CA 90089; FAU - Hoshino, Katsuaki AU - Hoshino K AD - Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Laboratory for Immune Regulation, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Department of Immunology, Faculty of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan; FAU - Kaisho, Tsuneyasu AU - Kaisho T AD - Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan; Department of Allergy and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory for Inflammatory Regulation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; 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; takaharu.okada@riken.jp tkaisho@wakayama-med.ac.jp. FAU - Okada, Takaharu AU - Okada T AD - Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama, Saitama 332-0012, Japan; Graduate School of Medical Life Science, Yokohama City University, Yokohama 230-0045, Japan takaharu.okada@riken.jp tkaisho@wakayama-med.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160111 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Antigens, CD) RN - 0 (Integrin alpha Chains) RN - 0 (Receptors, Chemokine) RN - 0 (XC chemokine receptor 1, mouse) RN - 0 (alpha E integrins) SB - IM MH - Animals MH - Antigens, CD/analysis MH - CD8-Positive T-Lymphocytes/immunology MH - Cell Movement MH - *Cross-Priming MH - Dendritic Cells/*immunology MH - Immunization MH - Integrin alpha Chains/analysis MH - Lymph Nodes/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Receptors, Chemokine/analysis/physiology MH - Skin/*immunology PMC - PMC4743831 OTO - NOTNLM OT - CD8+ T cell OT - cross-presentation OT - dendritic cell OT - intravital two-photon imaging OT - photoconversion COIS- The authors declare no conflict of interest. EDAT- 2016/01/13 06:00 MHDA- 2016/06/18 06:00 PMCR- 2016/01/11 CRDT- 2016/01/13 06:00 PHST- 2016/01/13 06:00 [entrez] PHST- 2016/01/13 06:00 [pubmed] PHST- 2016/06/18 06:00 [medline] PHST- 2016/01/11 00:00 [pmc-release] AID - 1513607113 [pii] AID - 201513607 [pii] AID - 10.1073/pnas.1513607113 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):1044-9. doi: 10.1073/pnas.1513607113. Epub 2016 Jan 11.