Ontogenic, Phenotypic, and Functional Characterization of XCR1(+) Dendritic Cells Leads to a Consistent Classification of Intestinal Dendritic Cells Based on the Expression of XCR1 and SIRPα.

Ontogenic, Phenotypic, and Functional Characterization of XCR1(+) Dendritic Cells Leads to a Consistent Classification of Intestinal Dendritic Cells Based on the Expression of XCR1 and SIRPα.
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DOI:
10.3389/fimmu.2014.00326
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发表时间:
2014
影响因子:
7.3
通讯作者:
Kroczek RA
Kroczek RA
中科院分区:
医学2区
文献类型:
--
作者:
Becker M;Güttler S;Bachem A;Hartung E;Mora A;Jäkel A;Hutloff A;Henn V;Mages HW;Gurka S;Kroczek RA

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过去,谱系标记的缺乏混淆了肠道中树突状细胞(DC)的分类,并阻碍了对其位置和功能的充分了解。我们最近发现趋化因子受体 XCR1 是脾脏中交叉呈递 DC 的谱系标记。现在,我们提供的证据表明,肠道 XCR1+ DC 很大程度上但不完全与 CD103+ CD11b− DC(肠道中“交叉呈递 DC”的假设相关)重叠,并且其发育选择性地依赖于转录因子 Batf3。 XCR1+ DC 位于小肠固有层的绒毛、派尔氏淋巴结的 T 细胞区以及引流肠系膜淋巴结的 T 细胞区和窦中。从功能上讲,我们首次证明 XCR1+/CD103+ CD11b− DC 在口服抗原的交叉呈递方面表现出色。总之,我们的数据表明 XCR1 也是肠道免疫系统中交叉呈递 DC 的谱系标记。此外,广泛的表型分析表明,整合素 SIRPα 的表达一致地划分了 XCR1−DC 群体。我们基于 XCR1 和 SIRPα 的表达提出了一个简化且一致的肠道 DC 分类系统。
In the past, lack of lineage markers confounded the classification of dendritic cells (DC) in the intestine and impeded a full understanding of their location and function. We have recently shown that the chemokine receptor XCR1 is a lineage marker for cross-presenting DC in the spleen. Now, we provide evidence that intestinal XCR1+ DC largely, but not fully, overlap with CD103+ CD11b− DC, the hypothesized correlate of “cross-presenting DC” in the intestine, and are selectively dependent in their development on the transcription factor Batf3. XCR1+ DC are located in the villi of the lamina propria of the small intestine, the T cell zones of Peyer’s patches, and in the T cell zones and sinuses of the draining mesenteric lymph node. Functionally, we could demonstrate for the first time that XCR1+/CD103+ CD11b− DC excel in the cross-presentation of orally applied antigen. Together, our data show that XCR1 is a lineage marker for cross-presenting DC also in the intestinal immune system. Further, extensive phenotypic analyses reveal that expression of the integrin SIRPα consistently demarcates the XCR1− DC population. We propose a simplified and consistent classification system for intestinal DC based on the expression of XCR1 and SIRPα.
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