Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität (LMU), 80336 Munich, Germany.
Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Biopolis, 138648 Singapore.
Sci Immunol. 2019 Jun 21;4(36). doi: 10.1126/sciimmunol.aar3054.
The role of nonclassical monocytes (NCMs) in health and disease is emerging, but their location and function within tissues remain poorly explored. Imaging of NCMs has been limited by the lack of an established single NCM marker. Here, we characterize the immune checkpoint molecule PD-L1 (CD274) as an unequivocal marker for tracking NCMs in circulation and pinpoint their compartmentalized distribution in tissues by two-photon microscopy. Visualization of PD-L1 NCMs in relation to bone marrow vasculature reveals that conversion of classical monocytes into NCMs requires contact with endosteal vessels. Furthermore, PD-L1 NCMs are present in tertiary lymphoid organs (TLOs) under inflammatory conditions in both mice and humans, and NCMs exhibit a PD-L1-dependent immunomodulatory function that promotes T cell apoptosis within TLOs. Our findings establish an unambiguous tool for the investigation of NCMs and shed light on their origin and function.
非经典单核细胞（NCMs）在健康和疾病中的作用正在显现，但它们在组织中的位置和功能仍未得到充分探索。由于缺乏已建立的单一 NCM 标志物，因此对 NCM 的成像受到限制。在这里，我们将免疫检查点分子 PD-L1（CD274）鉴定为一种明确的标记物，用于在循环中追踪 NCM，并通过双光子显微镜确定其在组织中的分区分布。与骨髓血管相关的 PD-L1 NCM 的可视化表明，经典单核细胞向 NCM 的转化需要与骨内膜血管接触。此外，在炎症条件下，PD-L1 NCM 存在于小鼠和人类的三级淋巴器官（TLO）中，并且 NCM 表现出依赖 PD-L1 的免疫调节功能，可促进 TLO 内 T 细胞凋亡。我们的发现为 NCM 的研究提供了一种明确的工具，并阐明了它们的起源和功能。
