Gradients of the signaling lipid S1P in lymph nodes position natural killer cells and regulate their interferon-gamma response

Fang Victoria; Chaluvadi V. Sai; Ramos-Perez Willy D.; Mendoza Alejandra; Baeyens Audrey; Rivera Richard; Chun Jerold; Cammer Michael; Schwab Susan R.

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Gradients of the signaling lipid S1P in lymph nodes position natural killer cells and regulate their interferon-gamma response

机译：淋巴结中的信号脂质S1p的梯度位置自然杀伤细胞并调节其干扰素-γ响应

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The lymph node periphery is an important site for many immunological functions, from pathogen containment to the differentiation of helper T cells, yet the cues that position cells in this region are largely undefined. Here, through the use of a reporter for the signaling lipid SIP (sphingosine 1-phosphate), we found that cells sensed higher concentrations of SIP in the medullary cords than in the T cell zone and that the S1P transporter SPNS2 on lymphatic endothelial cells generated this gradient. Natural killer (NK) cells are located at the periphery of the lymph node, predominantly in the medulla, and we found that expression of SPNS2, expression of the SIP receptor S1PR5 on NK cells, and expression of the chemokine receptor CXCR4 were all required for NK cell localization during homeostasis and rapid production of interferon-gamma by NK cells after challenge. Our findings elucidate the spatial cues for NK cell organization and reveal a previously unknown role for SIP in positioning cells within the medulla.

机译：淋巴结周边是许多免疫功能的重要部位，从病原体含量到辅助T细胞的分化，但该区域中位置细胞的提示大大未定义。这里，通过使用用于信号脂质SIP的记者（鞘氨醇1-磷酸），我们发现细胞感测了比T细胞区中的髓鞘帘线中更高浓度的SIP，并且S1P转运仪SPNS2产生的淋巴内皮细胞这个渐变。自然杀伤（NK）细胞位于淋巴结的周边，主要在髓质中，我们发现SPNS2的表达，SIP受体S1PR5对NK细胞的表达，以及趋化因子受体CXCR4的表达都是所必需的NK细胞定位在攻读期间，攻击后NK细胞快速生产干扰素-γ。我们的研究结果阐明了NK细胞组织的空间提示，并揭示了SIP在髓质内定位细胞中的先前未知的作用。

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《Nature immunology》 |2017年第1期|共11页
作者
Fang Victoria; Chaluvadi V. Sai; Ramos-Perez Willy D.; Mendoza Alejandra; Baeyens Audrey; Rivera Richard; Chun Jerold; Cammer Michael; Schwab Susan R.;
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NYU Sch Med Skirball Inst Biomol Med New York NY 10012 USA;

NYU Sch Med Skirball Inst Biomol Med New York NY 10012 USA;

NYU Sch Med Skirball Inst Biomol Med New York NY 10012 USA;

NYU Sch Med Skirball Inst Biomol Med New York NY 10012 USA;

NYU Sch Med Skirball Inst Biomol Med New York NY 10012 USA;

Scripps Res Inst Dorris Neurosci Ctr Dept Mol &

Cellular Neurosci La Jolla CA 92037 USA;

Scripps Res Inst Dorris Neurosci Ctr Dept Mol &

Cellular Neurosci La Jolla CA 92037 USA;

NYU Langone Med Ctr Microscopy Core Off Collaborat Sci New York NY USA;

NYU Sch Med Skirball Inst Biomol Med New York NY 10012 USA;

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正文语种 eng
中图分类医学免疫学;
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1. Gradients of the signaling lipid S1P in lymph nodes position natural killer cells and regulate their interferon-gamma response [J] . Fang Victoria, Chaluvadi V. Sai, Ramos-Perez Willy D., Nature immunology . 2017,第1期

机译：淋巴结中的信号脂质S1p的梯度位置自然杀伤细胞并调节其干扰素-γ响应
2. Pro- and antiinflammatory cytokine signaling: reciprocal antagonism regulates interferon-gamma production by human natural killer cells. [J] . Yu J, Wei M, Becknell B, Immunity . 2006,第5期

机译：促炎和抗炎细胞因子信号传导：相互拮抗作用调节人类自然杀伤细胞产生的干扰素-γ。
3. Retinoic Acid Modulates Interferon-gamma Production by Hepatic Natural Killer T Cells via Phosphatase 2A and the Extracellular Signal-Regulated Kinase Pathway [J] . Chang Heng-Kwei, Hou Wu-Shiun Journal of interferon and cytokine research: The official journal of the International Society for Interferon and Cytokine Research . 2015,第3期

机译：维甲酸通过磷酸酶2A和细胞外信号调节的激酶途径调节肝天然杀伤T细胞的干扰素γ生产。
4. Natural Killer Cell Engineering for Therapeutic Targeting of Metastases in the Tumor Draining Lymph Nodes [C] . Zheniiang Zhang, Dai Liu, Joshua D. Greenlee, Society for Biomaterials annual meeting and exposition . 2018

机译：治疗肿瘤引流淋巴结转移的靶向治疗的自然杀伤细胞工程。
5. The signals that regulate cytokine production by natural killer T cells. [D] . Nagarajan, Niranjana Aditi. 2005

机译：调节自然杀伤性T细胞产生细胞因子的信号。
6. Lymph node S1P gradients position natural killer cells and regulate their interferon-γ response [O] . Victoria Fang, V. Sai Chaluvadi, Willy D. Ramos-Perez, -1

机译：淋巴结S1P梯度定位自然杀伤细胞并调节其干扰素-γ反应
7. Gradients of the signaling lipid S1P in lymph nodes position natural killer cells and regulate their interferon-γ response [O] . Victoria Fang, V Sai Chaluvadi, Willy D Ramos-Perez, 2016

机译：淋巴结中的信号脂质S1p的梯度位置自然杀伤细胞并调节其干扰素-γ响应

Gradients of the signaling lipid S1P in lymph nodes position natural killer cells and regulate their interferon-gamma response

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