莫纳什大学Mariapia A. Degli-Esposti团队的一项最新研究探明了成纤维网状细胞通过CD44引导T细胞应答的启动。该项研究成果发表在2026年1月21日出版的《自然》上。

在这里，该课题组研究人员发现由疱疹病毒小鼠巨细胞病毒（CMV）编码的病毒蛋白m11通过靶向FRC网络和干扰细胞CD44的关键功能来抑制抗病毒免疫。研究人员发现m11与CD44结合，并确定m11干扰CD44与其天然配体透明质酸的分子相互作用。m11与CD44的相互作用损害了脾脏内树突状细胞的运输，从而阻碍了初始T细胞的有效启动和抗病毒CD8 T细胞反应的启动。CMV靶向CD44揭示了CD44作为FRC网络功能必不可少的分子，并揭示了以前未被识别的基于基质的机制，该机制对于产生有效的T细胞应答至关重要。

据介绍，树突状细胞和T细胞在次级淋巴器官内的运动对适应性免疫反应的发展至关重要。这一过程的核心是成纤维网状细胞（FRC）网络，它形成了一个高度组织化的导管系统，促进树突状细胞和T细胞之间的运动和相互作用。先前的研究已经部分描述了FRCs如何支持这些相互作用。然而，在生理条件下起作用的分子机制尚不清楚。

附：英文原文

Title: Fibroblastic reticular cells direct the initiation of T cell responses via CD44

Author: Sng, Xavier Y. X., Voigt, Valentina, Schuster, Iona S., Fleming, Peter, Deuss, Felix A., Abuwarwar, Mohammed H., van Dommelen, Serani L. H., Neate, Georgia E. G., Arnold, Riley M., Horsnell, Harry L., Daly, Sheridan, Golzarroshan, Bagher, Varelias, Antiopi, Lyman, Stewart D., Scalzo, Anthony A., Hill, Geoffrey R., Mueller, Scott N., Wikstrom, Matthew E., Berry, Richard, Rossjohn, Jamie, Fletcher, Anne L., Andoniou, Christopher E., Degli-Esposti, Mariapia A.

Issue&Volume: 2026-01-21

Abstract: The movement of dendritic cells and T cells within secondary lymphoid organs is critical for the development of adaptive immune responses1,2. Central to this process is the fibroblastic reticular cell (FRC) network, which forms a highly organized conduit system that facilitates the movement of and interactions between dendritic cells and T cells3,4,5,6. Previous studies have partly characterized how FRCs support these interactions7,8. However, the molecular mechanisms that operate under physiological conditions remain unknown. Here we show that the viral protein m11, encoded by the herpesvirus murine cytomegalovirus (CMV), inhibits antiviral immunity by targeting the FRC network and interfering with a critical function of cellular CD44. We found that m11 binds to CD44 and established that m11 perturbs the molecular interactions of CD44 with its natural ligand, hyaluronic acid. The interaction of m11 with CD44 impairs the trafficking of dendritic cells within the spleen, thereby impeding efficient priming of naive T cells and the initiation of antiviral CD8 T cell responses. The targeting of CD44 by CMV reveals CD44 as a molecule that is essential to the functioning of the FRC network and uncovers a previously unrecognized stroma-based mechanism that is critical for the generation of effective T cell responses.

DOI: 10.1038/s41586-025-09988-8

Source: https://www.nature.com/articles/s41586-025-09988-8