Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids.

Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids.
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DOI:
10.1371/journal.pbio.0030113
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发表时间:
2005-04
期刊:
影响因子:
9.8
通讯作者:
Littman DR
Littman DR
中科院分区:
生物学1区
文献类型:
--
作者:
Geissmann F;Cameron TO;Sidobre S;Manlongat N;Kronenberg M;Briskin MJ;Dustin ML;Littman DR

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我们使用绿色荧光蛋白cDNA取代编码趋化因子受体CXCR6的基因,通过活体荧光显微成像检测了小鼠肝脏自然杀伤T细胞(NKT细胞)的体内行为。NKT细胞以10 ~ 20 μm/min的速度在肝窦内爬行,并在T细胞抗原受体激活时停止,是肝脏中CXCR6+细胞的主要组成部分。cxcr6缺陷小鼠表现出肝脏中cd1反应性NKT细胞的选择性和严重减少,并且对t细胞依赖性肝炎的易感性降低。CXCR6的细胞表面配体CXCL16在窦状内皮细胞上表达,CXCR6缺乏导致存活降低,但不会改变NKT细胞的巡逻速度或模式。因此,NKT细胞在肝窦内巡逻,提供血管内免疫监视,而CXCR6通过调节其丰富度参与肝脏免疫应答。活体荧光显微镜显示,自然杀伤T细胞在肝脏血管中巡逻并在激活时停止,证明了它们在肝脏免疫监视中的作用
We examined the in vivo behavior of liver natural killer T cells (NKT cells) by intravital fluorescence microscopic imaging of mice in which a green fluorescent protein cDNA was used to replace the gene encoding the chemokine receptor CXCR6. NKT cells, which account for most CXCR6+ cells in liver, were found to crawl within hepatic sinusoids at 10–20 μm/min and to stop upon T cell antigen receptor activation. CXCR6-deficient mice exhibited a selective and severe reduction of CD1d-reactive NKT cells in the liver and decreased susceptibility to T-cell-dependent hepatitis. CXCL16, the cell surface ligand for CXCR6, is expressed on sinusoidal endothelial cells, and CXCR6 deficiency resulted in reduced survival, but not in altered speed or pattern of patrolling of NKT cells. Thus, NKT cells patrol liver sinusoids to provide intravascular immune surveillance, and CXCR6 contributes to liver-based immune responses by regulating their abundance. Intravital fluorescence microscopy shows that natural killer T cells patrol blood vessels in the liver and stop upon activation, demonstrating their role in liver immune surveillance
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