2026年4月23日出版的《免疫学》杂志发表了瑞士科学家的一项最新研究成果。来自洛桑大学的Sanjiv A. Luther小组发现了稳态成熟树突状细胞通过Notch2信号指导成纤维细胞特化以建立T细胞生态位。

该课题组研究了驱动FRC分化成功能不同子集的途径。Notch信号可以区分淋巴结（LN） FRCs，而FRCs中Notch1和Notch2的缺失限制了功能特化，尤其是T区FRCs（T区网状细胞[TRCs]）。树突状细胞（DC）特异性的Notch配体Jagged-1的缺失阻止了Ccl19^hi TRC的分化，同时也需要稳态Ccr7⁺ DC来维持其分化。由此产生的Ccl19趋化因子表达支持Xcr1⁺ DCs和CD8⁺ T细胞中富集的中央T区亚室的形成。空间组织和Notch2-Jagged1信号活性在人类LNs中都是保守的。在FRCs中通过Notch2失活破坏T区分离会损害CD8⁺ T细胞记忆前体的生成。然后，DCs通过Notch2依赖性TRC编程形成不同的T区小生境，维持CD8⁺ T细胞免疫。

据了解，次级淋巴器官的区隔化是由专门的纤维母细胞网状细胞（FRCs）精心安排的，它指导免疫细胞的迁移、相互作用和功能。

附：英文原文

Title: Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 signaling to establish T cell niches

Author: Nagham Alouche, Hélène Cannelle, Stéphanie Favre, Marija Joki, José A. Villegas, Sandra Maréchal, Clint De Nolf, Maeva Delacrétaz, Alexandros Sifis, Chloé Chapuis, Allison Burns, Giovanna Ambrosini, Isabelle Dupanloup, Jun Abe, Ute Koch, Nicolas Guex, Jens V. Stein, Ivan Maillard, Tom Cupedo, Burkhard Ludewig, Freddy Radtke, Sophie Janssens, Sanjiv A. Luther

Issue&Volume: 2026-04-23

Abstract: Compartmentalization of secondary lymphoid organs is orchestrated by specialized fibroblastic reticular cells (FRCs), which guide immune cell migration, interaction, and function. Here, we investigated the pathways driving FRC differentiation into functionally distinct subsets. A Notch signaling signature distinguished lymph node (LN) FRCs, and deletion of Notch1 and Notch2 in FRCs restricted functional specialization, particularly for T-zone FRCs (T-zone reticular cells [TRCs]). Dendritic cell (DC)-specific deletion of the Notch ligand Jagged-1 prevented Ccl19hi TRC differentiation, with homeostatic Ccr7+ DCs also being required for their maintenance. The resulting Ccl19 chemokine expression supported formation of central T-zone sub-compartments enriched in Xcr1+ DCs and CD8+ T cells. Both the spatial organization and Notch2-Jagged1 signaling activity were conserved in human LNs. Disrupting T-zone segregation via Notch2 inactivation in FRCs impaired the generation of CD8+ T cell memory precursors. Thus, Notch2-dependent TRC programming by DCs shapes distinct T-zone niches that sustain CD8+ T cell immunity.

DOI: 10.1016/j.immuni.2026.03.023

Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00134-2