Department of Biochemistry and Molecular Biology, and Monash Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Eur J Immunol. 2023 Sep;53(9):e2250355. doi: 10.1002/eji.202250355. Epub 2023 Jul 12.
The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models. Macrophages co-localized with FRCs in human LNs, and murine single-cell RNA-sequencing revealed that FRC subsets broadly expressed master macrophage regulator CSF1. Functional assays containing purified FRCs and monocytes showed that CSF1R signaling was sufficient to support macrophage development. These effects were conserved between mouse and human systems. These data indicate an important role for FRCs in maintaining the LN parenchymal macrophage niche.
淋巴结（LN）是驻留巨噬细胞群体的家园，这些群体对于免疫功能和体内平衡至关重要，但控制这个小生境的关键因素尚未确定。在这里，我们表明纤维母细胞网状细胞（FRCs）是 LN 巨噬细胞小生境的重要组成部分。在两种体内模型中，FRC 的遗传消融导致巨噬细胞和单核细胞从 LNs 中迅速丢失。巨噬细胞与人 LNs 中的 FRC 共定位，而小鼠单细胞 RNA 测序显示 FRC 亚群广泛表达巨噬细胞主调控因子 CSF1。包含纯化的 FRC 和单核细胞的功能测定表明 CSF1R 信号足以支持巨噬细胞的发育。这些效应在小鼠和人类系统之间是保守的。这些数据表明 FRCs 在维持 LN 实质巨噬细胞小生境方面起着重要作用。
