Critical Roles of a Dendritic Cell Subset Expressing a Chemokine Receptor, XCR1
Critical Roles of a Dendritic Cell Subset Expressing a Chemokine Receptor, XCR1
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DOI：
10.4049/jimmunol.1202798
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发表时间：
2013-06
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通讯作者：
C. Yamazaki;Masanaka Sugiyama;Tomokazu Ohta;H. Hemmi;Eri Hamada;I. Sasaki;Yuri Fukuda;T. Yano;Mikako Nobuoka;Takeshi Hirashima;A. Iizuka;Katsuaki Sato;Takashi Tanaka;K. Hoshino;T. Kaisho
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作者：
C. Yamazaki;Masanaka Sugiyama;Tomokazu Ohta;H. Hemmi;Eri Hamada;I. Sasaki;Yuri Fukuda;T. Yano;Mikako Nobuoka;Takeshi Hirashima;A. Iizuka;Katsuaki Sato;Takashi Tanaka;K. Hoshino;T. Kaisho
树突状细胞（Dendritic cells，DC）是一组在天然免疫和适应性免疫中起重要作用的细胞亚群。在小鼠脾脏中，CD 8 α+ DC表现出摄取垂死/死亡细胞、产生促炎细胞因子和交叉呈递Ag以产生CD 8 + T细胞应答的倾向。为了在体内追踪和消融CD 8 α+ DCs，我们产生了XCR 1-venus和XCR 1-DTR venus小鼠，其中荧光蛋白venus和白喉毒素受体和venus组成的融合蛋白的基因被敲入趋化因子受体XCR 1的基因位点，XCR 1在CD 8 α+ DCs中高度表达。在这两种小鼠中，在大多数CD 8 α+ DC中检测到venus+细胞，但在任何其他细胞（包括脾巨噬细胞）中均未检测到venus+细胞。Venus+ CD 8 α+ DCs在对TLR刺激的反应中产生精氨酸的能力上级venus− CD 8 α+ DCs。在其他组织中，静脉阳性细胞主要存在于淋巴结（LN）驻留的CD 8 α+、LN迁移和外周CD 103 + DC中，这些DC与脾脏CD 8 α+ DC密切相关，尽管一些胸腺CD 8 α− CD 11b −和LN CD 103 − CD 11b − DC也是静脉阳性。在对dsRNA的应答中，白喉毒素处理的XCR 1-DTR小鼠显示出受损的CD 8 + T细胞应答，保留细胞因子和增强的CD 4 + T细胞应答。此外，单核细胞增生李斯特菌感染和抗-L。在白喉毒素处理的XCR 1-DTRvenus小鼠中单核细胞增生性CD 8 + T细胞应答是缺陷的。因此，表达XCR 1的DC是dsRNA或细菌诱导的CD 8 + T细胞应答所必需的。XCR 1-venus和XCR 1-DTR venus小鼠可用于阐明表达XCR 1的DC（包括CD 8 α+和CD 103 + DC）在淋巴和外周组织中的功能和行为。
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.