Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis.
Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis.
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DOI：
10.1038/srep23505
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发表时间：
2016-03-23
影响因子：
4.6
通讯作者：
Kaisho T
中科院分区：
文献类型：
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作者：
Ohta T;Sugiyama M;Hemmi H;Yamazaki C;Okura S;Sasaki I;Fukuda Y;Orimo T;Ishii KJ;Hoshino K;Ginhoux F;Kaisho T
肠道免疫动态平衡需要先天免疫细胞和获得性免疫细胞之间的动态串扰。树突状细胞(DC)以多种表型和功能不同的亚群存在于组织内，在那里它们启动免疫反应并促进内环境稳定。在肠道中，存在一个被定义为CD103+CD11b−的DC亚群，它也表达趋化因子受体XCR1。在其他组织中，XCR1+DC交叉呈递抗原，有助于抗病毒和癌症的免疫，但XCR1+DC和XCR1在肠道中的作用尚不清楚。我们发现，缺乏XCR1+DC的小鼠在上皮内和固有层(LP)T细胞群中特异性不足，剩余的T细胞表现出不典型的表型，容易死亡，也更容易患上化学诱导的结肠炎。同样，缺乏XCR1或其配体XCL1的小鼠的肠道T细胞数量减少，肠道中XCR1+DC积聚。结合转录组和表面标志物的表达分析，这些观察结果导致我们假设T细胞来源的XCL1促进肠道XCR1+DC的激活和迁移，而XCR1+DC反过来为T细胞的生存和功能提供支持。因此，XCR1+DC和XCR1/XCL1趋化素轴在肠道免疫动态平衡中具有以前未被认识到的作用。
Intestinal immune homeostasis requires dynamic crosstalk between innate and adaptive immune cells. Dendritic cells (DCs) exist as multiple phenotypically and functionally distinct sub-populations within tissues, where they initiate immune responses and promote homeostasis. In the gut, there exists a minor DC subset defined as CD103+CD11b− that also expresses the chemokine receptor XCR1. In other tissues, XCR1+ DCs cross-present antigen and contribute to immunity against viruses and cancer, however the roles of XCR1+ DCs and XCR1 in the intestine are unknown. We showed that mice lacking XCR1+ DCs are specifically deficient in intraepithelial and lamina propria (LP) T cell populations, with remaining T cells exhibiting an atypical phenotype and being prone to death, and are also more susceptible to chemically-induced colitis. Mice deficient in either XCR1 or its ligand, XCL1, similarly possess diminished intestinal T cell populations, and an accumulation of XCR1+ DCs in the gut. Combined with transcriptome and surface marker expression analysis, these observations lead us to hypothesise that T cell-derived XCL1 facilitates intestinal XCR1+ DC activation and migration, and that XCR1+ DCs in turn provide support for T cell survival and function. Thus XCR1+ DCs and the XCR1/XCL1 chemokine axis have previously-unappreciated roles in intestinal immune homeostasis.