德国路德维希-马克西米利安-慕尼黑大学Christoph Scheiermann小组的研究显示，生物钟调控树突细胞进入皮肤淋巴管 (LV) 。相关论文于2021年10月18日发表于国际学术期刊《自然-免疫学》杂志。

在本研究中，研究人员揭示了树突状细胞(DC)具有进入LV的昼夜节律迁移模式，该迁移在小鼠休息阶段达到峰值。这种迁移模式是由小鼠和人趋化因子CCL21和粘附分子表达的节律梯度所决定。对相关因素的时间药理学抑制导致DC的昼夜节律迁移消失。研究人员确定了皮肤淋巴管内皮细胞(LEC)和DC中的细胞内在昼夜节律，它们共同控制这些节律，因为利用遗传方法破坏任一细胞类型中的节律都会消除DC的昼夜节律迁移。这些观察结果表明，生物钟控制着DCs向皮肤淋巴管的浸润，这一过程对于许多适应性免疫反应至关重要，并且与疫苗接种和免疫疗法相关。 

据了解，白细胞通过传入LV从皮肤迁移到淋巴结(LN)是适应性免疫反应的关键。昼夜节律已成为白细胞通过血液运输到LN的重要调节因素。

附：英文原文

Title: Circadian clocks guide dendritic cells into skin lymphatics

Author: Holtkamp, Stephan J., Ince, Louise M., Barnoud, Coline, Schmitt, Madeleine T., Sinturel, Flore, Pilorz, Violetta, Pick, Robert, Jemelin, Stphane, Mhlstdt, Michael, Boehncke, Wolf-Henning, Weber, Jasmin, Laubender, David, Philippou-Massier, Julia, Chen, Chien-Sin, Holtermann, Leonie, Vestweber, Dietmar, Sperandio, Markus, Schraml, Barbara U., Halin, Cornelia, Dibner, Charna, Oster, Henrik, Renkawitz, Jrg, Scheiermann, Christoph

Issue&Volume: 2021-10-18

Abstract: Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses1,2. Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood3,4. Here, we demonstrate that dendritic cells (DCs) have a circadian migration pattern into LVs, which peaks during the rest phase in mice. This migration pattern is determined by rhythmic gradients in the expression of the chemokine CCL21 and of adhesion molecules in both mice and humans. Chronopharmacological targeting of the involved factors abrogates circadian migration of DCs. We identify cell-intrinsic circadian oscillations in skin lymphatic endothelial cells (LECs) and DCs that cogovern these rhythms, as their genetic disruption in either cell type ablates circadian trafficking. These observations indicate that circadian clocks control the infiltration of DCs into skin lymphatics, a process that is essential for many adaptive immune responses and relevant for vaccination and immunotherapies. Scheiermann and colleagues show that circadian clocks control the infiltration of dendritic cells into skin lymphatics in mice and humans, with a peak migration to the lymph nodes during the rest phase.

DOI: 10.1038/s41590-021-01040-x

Source: https://www.nature.com/articles/s41590-021-01040-x