Monocyte-derived S1P in the lymph node regulates immune responses.
Monocyte-derived S1P in the lymph node regulates immune responses.
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DOI：
10.1038/s41586-021-03227-6
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发表时间：
2021-04
期刊：
影响因子：
64.8
通讯作者：
Schwab SR
中科院分区：
文献类型：
--
作者：
Baeyens A;Bracero S;Chaluvadi VS;Khodadadi-Jamayran A;Cammer M;Schwab SR
脂类趋化物质1-磷酸鞘氨醇(S1P)引导细胞从组织的低S1P环境进入循环液的高S1P环境。值得注意的是，S1P引导T细胞从最初被激活的淋巴结(LN)退出，进入淋巴，T细胞从淋巴进入血液，最终到达炎症组织。T细胞主要通过S1P受体1(S1PR1)跟随S1P梯度。虽然最近的工作描述了S1P梯度是如何在稳定状态建立的，但关于S1P在疾病中的分布，或者S1P水平的变化如何影响免疫反应，人们知之甚少。在这里，我们发现在免疫反应期间LN中S1P浓度增加。造血细胞，包括炎性单核细胞(IMO)，是这种S1P的重要来源，这是一个意想不到的发现，因为内皮细胞提供淋巴S1P。IMO需要早期激活标记CD69来提供这种S1P，部分原因是CD69的表达与S1pr5水平的降低有关。CD69作为一种“站稳脚跟”的信号，通过调节S1P受体和S1P梯度，将免疫细胞保持在炎症部位。最后，S1P的增加延长了T细胞在LN中的停留时间，加重了实验性自身免疫性脑脊髓炎的严重程度。这一发现提出了LN滞留时间调节T细胞分化的假设，并指出了针对S1P信号转导的药物的新用途。
The lipid chemoattractant sphingosine 1-phosphate (S1P) guides cells from the low-S1P environment of tissues into the high-S1P environment of circulatory fluids. Notably, S1P directs T cell exit from lymph nodes (LN), where T cells are initially activated, into lymph, from which T cells reach blood and ultimately inflamed tissues. T cells follow S1P gradients primarily using S1P receptor 1 (S1PR1). While recent work has described how S1P gradients are established at steady-state, little is known about S1P distribution in disease, or about how changing S1P levels may affect immune responses. Here, we find that S1P concentrations increase in LN during an immune response. Hematopoietic cells, including inflammatory monocytes (iMo), are an important source of this S1P, an unexpected finding as endothelial cells provide lymph S1P. iMo require the early activation marker CD69 to supply this S1P, in part because CD69 expression is associated with reduced levels of S1pr5. CD69 acts as a “stand-your-ground” signal, keeping immune cells at a site of inflammation by regulating both S1P receptors and S1P gradients. Finally, increased S1P prolongs T cell residence time in LN, and exacerbates the severity of experimental autoimmune encephalomyelitis. This finding suggests the hypothesis that LN residence time regulates T cell differentiation, and points to novel uses of drugs targeting S1P signaling.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
30.3
作者：
Hohl TM;Rivera A;Lipuma L;Gallegos A;Shi C;Mack M;Pamer EG
通讯作者：
Pamer EG
影响因子：
32.4
作者：
Lee, June-Yong;Skon, Cara N.;Lee, You Jeong;Oh, Soohwan;Taylor, Justin J.;Malhotra, Deepali;Jenkins, Marc K.;Rosenfeld, M. Geoffrey;Hogquist, Kristin A.;Jameson, Stephen C.
通讯作者：
Jameson, Stephen C.
DOI：
10.1084/jem.20041509
发表时间：
2005-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lo CG;Xu Y;Proia RL;Cyster JG
通讯作者：
Cyster JG