小柯机器人

美国纽约大学兰贡医学中心Susan R. Schwab课题组在研究中取得进展。他们表明淋巴结中单核细胞来源的1-磷酸鞘氨醇（S1P）调节免疫反应。2021年3月3日国际知名学术期刊《自然》杂志发表了这一成果。

他们显示免疫反应期间淋巴结中S1P的浓度增加。他们发现造血细胞，包括炎性单核细胞，是这种S1P的重要来源，这是一个出乎意料的发现，因为内皮细胞向淋巴提供了S1P。炎性单核细胞需要早期激活标记CD69来提供S1P，部分原因是CD69的表达与S1pr5（编码S1P受体5）的水平降低有关。CD69充当“坚守阵地”的信号，通过调节S1P的受体和梯度将免疫细胞保持在炎症部位。最后，S1P水平升高会延长T细胞在淋巴结中的停留时间，并加剧小鼠实验性自身免疫性脑脊髓炎的严重程度。这一发现表明，在淋巴结中的停留时间可能会调节T细胞的分化，并指出靶向S1P信号传导的药物的新用途。

据了解，脂质化学引诱剂S1P将细胞从S1P浓度相对较低的组织引出到循环体液中，S1P浓度较高。例如，S1P引导T细胞从最初激活T细胞的淋巴结进入淋巴，然后T细胞到达血液并最终使组织发炎。T细胞主要利用S1P受体遵循S1P梯度。最近的研究描述了如何在稳态下建立S1P梯度，但对S1P在疾病中的分布或S1P水平的变化如何影响免疫反应的了解却很少。

附：英文原文

Title: Monocyte-derived S1P in the lymph node regulates immune responses

Author: Audrey Baeyens, Sabrina Bracero, Venkata S. Chaluvadi, Alireza Khodadadi-Jamayran, Michael Cammer, Susan R. Schwab

Issue&Volume: 2021-03-03

Abstract: The lipid chemoattractant sphingosine 1-phosphate (S1P) guides cells out of tissues, where the concentration of S1P is relatively low, into circulatory fluids, where the concentration of S1P is high1. For example, S1P directs the exit of T cells from lymph nodes, where T cells are initially activated, into lymph, from which T cells reach the blood and ultimately inflamed tissues1. T cells follow S1P gradients primarily using S1P receptor 1 (ref. 1). Recent studies have described how S1P gradients are established at steady state, but little is known about the distribution of S1P in disease or about how changing levels of S1P may affect immune responses. Here we show that the concentration of S1P increases in lymph nodes during an immune response. We found that haematopoietic cells, including inflammatory monocytes, were an important source of this S1P, which was an unexpected finding as endothelial cells provide S1P to lymph1. Inflammatory monocytes required the early activation marker CD69 to supply this S1P, in part because the expression of CD69 was associated with reduced levels of S1pr5 (which encodes S1P receptor 5). CD69 acted as a ‘stand-your-ground’ signal, keeping immune cells at a site of inflammation by regulating both the receptors and the gradients of S1P. Finally, increased levels of S1P prolonged the residence time of T cells in the lymph nodes and exacerbated the severity of experimental autoimmune encephalomyelitis in mice. This finding suggests that residence time in the lymph nodes might regulate the differentiation of T cells, and points to new uses of drugs that target S1P signalling.

DOI: 10.1038/s41586-021-03227-6

Source: https://www.nature.com/articles/s41586-021-03227-6

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