Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1

Chihiro Yamazaki, Masanaka Sugiyama, Tomokazu Ohta, Hiroaki Hemmi, Eri Hamada, Izumi Sasaki, Yuri Fukuda, Takahiro Yano, Mikako Nobuoka, Takeshi Hirashima, Akihiko Iizuka, Katsuaki Sato, Takashi Tanaka, Katsuaki Hoshino, Tsuneyasu Kaisho

Research output: Contribution to journalArticle

61 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6071-6082
Number of pages12
JournalJournal of Immunology
Volume190
Issue number12
DOIs
Publication statusPublished - Jun 15 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Yamazaki, C., Sugiyama, M., Ohta, T., Hemmi, H., Hamada, E., Sasaki, I., Fukuda, Y., Yano, T., Nobuoka, M., Hirashima, T., Iizuka, A., Sato, K., Tanaka, T., Hoshino, K., & Kaisho, T. (2013). Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1. Journal of Immunology, 190(12), 6071-6082. https://doi.org/10.4049/jimmunol.1202798