德国慕尼黑大学Konstantin Stark和Kami Pekayvaz共同合作，近期取得重要工作进展。他们研究发现，壁细胞来源的趋化因子为保护血管巨噬细胞并限制慢性炎症提供了保护性生态位。相关研究成果2023年8月30日在线发表于《免疫学》杂志上。

据介绍，适应不良、不消退的炎症会导致动脉粥样硬化等慢性炎症性疾病。由于巨噬细胞可以清除坏死细胞，有缺陷的巨噬细胞程序可以促进慢性炎症和持续的组织损伤。

研究人员探讨了维持血管巨噬细胞的机制。活体成像显示，血管床中存在一个时空巨噬细胞生态位，旁边还有壁细胞（MC），包括周细胞和平滑肌细胞。单细胞转录组学、共培养和基因缺失实验揭示了MC来源的趋化因子CCL2和MIF的表达，它们积极保护巨噬细胞的生存及其稳态功能。在动脉粥样硬化中，这将巨噬细胞定位在有活力的斑块区域，远离坏死核心，并保持稳态巨噬细胞表型。通过MC特异性趋化因子的缺失破坏这种MC-巨噬细胞单元，引发有害的巨噬细胞重新定位，加剧斑块坏死、炎症和动脉粥样硬化进展。

总之，CCL2在动脉粥样硬化晚期的抑制显示出有害的影响。这项工作提出了一种MC驱动的保护措施，以维持血管巨噬细胞生态位的稳态。

附：英文原文

Title: Mural cell-derived chemokines provide a protective niche to safeguard vascular macrophages and limit chronic inflammation

Author: Kami Pekayvaz, Christoph Gold, Parandis Hoseinpour, Anouk Engel, Alejandro Martinez-Navarro, Luke Eivers, Raffaele Coletti, Markus Joppich, Flávio Dionísio, Rainer Kaiser, Lukas Tomas, Aleksandar Janjic, Maximilian Knott, Fitsumbirhan Mehari, Vivien Polewka, Megan Kirschner, Annegret Boda, Leo Nicolai, Heiko Schulz, Anna Titova, Badr Kilani, Michael Lorenz, Günter Fingerle-Rowson, Richard Bucala, Wolfgang Enard, Ralf Zimmer, Christian Weber, Peter Libby, Christian Schulz, Steffen Massberg, Konstantin Stark

Issue&Volume: 2023-08-30

Abstract: Maladaptive, non-resolving inflammation contributes to chronic inflammatory diseases such as atherosclerosis. Because macrophages remove necrotic cells, defective macrophage programs can promote chronic inflammation with persistent tissue injury. Here, we investigated the mechanisms sustaining vascular macrophages. Intravital imaging revealed a spatiotemporal macrophage niche across vascular beds alongside mural cells (MCs)—pericytes and smooth muscle cells. Single-cell transcriptomics, co-culture, and genetic deletion experiments revealed MC-derived expression of the chemokines CCL2 and MIF, which actively preserved macrophage survival and their homeostatic functions. In atherosclerosis, this positioned macrophages in viable plaque areas, away from the necrotic core, and maintained a homeostatic macrophage phenotype. Disruption of this MC-macrophage unit via MC-specific deletion of these chemokines triggered detrimental macrophage relocalizing, exacerbated plaque necrosis, inflammation, and atheroprogression. In line, CCL2 inhibition at advanced stages of atherosclerosis showed detrimental effects. This work presents a MC-driven safeguard toward maintaining the homeostatic vascular macrophage niche.

DOI: 10.1016/j.immuni.2023.08.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00358-8