法国巴黎PSL大学Ana-Maria Lennon-Duménil和Matthieu Piel小组，报道了细胞形状感知允许树突状细胞向淋巴结进行同源迁移。2024年6月4日出版的《自然-免疫学》杂志发表了这一最新研究成果。

据悉，由于在组织中迁移时会遇到物理限制，免疫细胞在巡视环境过程中会经历复杂的细胞形状变化。这些细胞可以利用专门的形状感应途径来适应这种变形事件。然而，目前尚不清楚形状感应是如何影响免疫细胞功能的。

研究人员发现了一种形状感应机制，它能增加趋化因子受体CCR7的表达，并在稳定状态时引导树突状细胞从外周组织迁移到淋巴结。这种机制依赖于脂质代谢酶cPLA2，需要核膜张力，ARP2/3肌动蛋白成核复合物参与微调。

研究还发现，该形状感应通路通过激活IKKβ-NF-κB依赖性途径，对树突状细胞转录进行了重编程，该途径已知具有控制树突状细胞耐受性潜能。这些结果表明，由免疫细胞经历的细胞形状变化可以确定它们的迁移行为和免疫调节特性，并揭示了组织物理特性对适应性免疫的作用。

附：英文原文

Title: Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes

Author: Alraies, Zahraa, Rivera, Claudia A., Delgado, Maria-Graciela, Sansau, Doriane, Maurin, Mathieu, Amadio, Roberto, Maria Piperno, Giulia, Dunsmore, Garett, Yatim, Aline, Lacerda Mariano, Livia, Kniazeva, Anna, Calmettes, Vincent, Sez, Pablo J., Williart, Alice, Popard, Henri, Gratia, Matthieu, Lamiable, Olivier, Moreau, Aurlie, Fusilier, Zo, Crestey, Lou, Albaud, Benoit, Legoix, Patricia, Dejean, Anne S., Le Dorze, Anne-Louise, Nakano, Hideki, Cook, Donald N., Lawrence, Toby, Manel, Nicolas, Benvenuti, Federica, Ginhoux, Florent, Moreau, Hlne D., P. F. Nader, Guilherme, Piel, Matthieu, Lennon-Dumnil, Ana-Maria

Issue&Volume: 2024-06-04

Abstract: Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These cells can adapt to such deformation events using dedicated shape-sensing pathways. However, how shape sensing affects immune cell function is mostly unknown. Here, we identify a shape-sensing mechanism that increases the expression of the chemokine receptor CCR7 and guides dendritic cell migration from peripheral tissues to lymph nodes at steady state. This mechanism relies on the lipid metabolism enzyme cPLA2, requires nuclear envelope tensioning and is finely tuned by the ARP2/3 actin nucleation complex. We also show that this shape-sensing axis reprograms dendritic cell transcription by activating an IKKβ–NF-κB-dependent pathway known to control their tolerogenic potential. These results indicate that cell shape changes experienced by immune cells can define their migratory behavior and immunoregulatory properties and reveal a contribution of the physical properties of tissues to adaptive immunity.

DOI: 10.1038/s41590-024-01856-3

Source: https://www.nature.com/articles/s41590-024-01856-3