Alexandre Yannick O, Potemkin Nikita, Schienstock Dominik, Duchamp Baptiste, Poch Annika, Christo Susan N, Li Shihan, Qin Lei, Beattie Lynette, Utzschneider Daniel T, Ono Masahiro, Schröder Jan, Mackay Laura K, Mueller Scott N
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
Department of Life Sciences, Imperial College London, London, UK.
Sci Adv. 2025 Jun 6;11(23):eadt5939. doi: 10.1126/sciadv.adt5939. Epub 2025 Jun 4.
Fibroblastic reticular cells (FRCs) are specialized fibroblasts that construct secondary lymphoid organs where they provide crucial signals for immune cell homeostasis and migration. While splenic FRCs are thought to support antiviral T cell responses, their role remains unclear. Here, we found that ablation of splenic FRCs impaired virus-specific CD8 T cell responses during lymphocytic choriomeningitis virus (LCMV) infection. Immunofluorescence imaging revealed that FRCs promote CD8 T cell clustering with type 1 conventional dendritic cells (cDC1) in the T cell zone before migration to the infected marginal zone. Without FRCs, T cells instead clustered with cDC1 and virus-infected cells in the marginal zone, leading to suboptimal priming. Mechanistically, FRCs coordinated early viral replication and the inflammatory milieu for optimal DC activation, and an intact FRC network was crucial for generating effector T cells and maintaining protective memory T cells. Thus, splenic FRCs provide essential lymphoid niches for antiviral T cell responses.
成纤维网状细胞（FRCs）是一种特殊的成纤维细胞，它们构建二级淋巴器官，并在其中为免疫细胞的稳态和迁移提供关键信号。虽然脾脏FRCs被认为支持抗病毒T细胞反应，但其作用仍不清楚。在这里，我们发现脾脏FRCs的消融会损害淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染期间病毒特异性CD8 T细胞反应。免疫荧光成像显示，FRCs在迁移到受感染的边缘区之前，促进CD8 T细胞与T细胞区的1型传统树突状细胞（cDC1）聚集。没有FRCs时，T细胞反而在边缘区与cDC1和病毒感染细胞聚集，导致启动效果不佳。从机制上讲，FRCs协调早期病毒复制和炎症环境以实现最佳的DC激活，完整的FRC网络对于产生效应T细胞和维持保护性记忆T细胞至关重要。因此，脾脏FRCs为抗病毒T细胞反应提供了必不可少的淋巴微环境。
