title: Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1.
abstract: Dendritic cells (DCs) consist of various subsets that play crucial roles in linking innate and adaptive immunity. In the murine spleen, CD8α(+) DCs exhibit a propensity to ingest dying/dead cells, produce proinflammatory cytokines, and cross-present Ags to generate CD8(+) T cell responses. To track and ablate CD8α(+) DCs in vivo, we generated XCR1-venus and XCR1-DTRvenus mice, in which genes for a fluorescent protein, venus, and a fusion protein consisting of diphtheria toxin receptor and venus were knocked into the gene locus of a chemokine receptor, XCR1, which is highly expressed in CD8α(+) DCs. In both mice, venus(+) cells were detected in the majority of CD8α(+) DCs, but they were not detected in any other cells, including splenic macrophages. Venus(+)CD8α(+) DCs were superior to venus(-)CD8α(+) DCs with regard to their cytokine-producing ability in response to TLR stimuli. In other tissues, venus(+) cells were found primarily in lymph node (LN)-resident CD8α(+), LN migratory and peripheral CD103(+) DCs, which are closely related to splenic CD8α(+) DCs, although some thymic CD8α(-)CD11b(-) and LN CD103(-)CD11b(-) DCs were also venus(+). In response to dsRNAs, diphtheria toxin-treated XCR1-DTR mice showed impaired CD8(+) T cell responses, with retained cytokine and augmented CD4(+) T cell responses. Furthermore, Listeria monocytogenes infection and anti-L. monocytogenes CD8(+) T cell responses were defective in diphtheria toxin-treated XCR1-DTRvenus mice. Thus, XCR1-expressing DCs were required for dsRNA- or bacteria-induced CD8(+) T cell responses. XCR1-venus and XCR1-DTRvenus mice should be useful for elucidating the functions and behavior of XCR1-expressing DCs, including CD8α(+) and CD103(+) DCs, in lymphoid and peripheral tissues.
authors.affiliation: Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yamazaki
authors.forename: Masanaka
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Ohta
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hemmi
authors.forename: Eri
authors.initials: E
authors.lastname: Hamada
authors.forename: Izumi
authors.initials: I
authors.lastname: Sasaki
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yano
authors.forename: Mikako
authors.initials: M
authors.lastname: Nobuoka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirashima
authors.forename: Akihiko
authors.initials: A
authors.lastname: Iizuka
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Hoshino
authors.forename: Tsuneyasu
authors.initials: T
authors.lastname: Kaisho
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002469:Cell Separation; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D055879:Gene Knock-In Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019707:Receptors, Chemokine / Q000276:immunology* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D019707:Receptors, Chemokine; C551408:XC chemokine receptor 1, mouse; C054562:yellow fluorescent protein, Bacteria