加拿大大学健康网络Clinton S. Robbins研究团队发现，产生集落刺激因子-1的内皮细胞和间质基质细胞将单核细胞维持在血管周围的骨髓微环境中。2022年5月3日，《免疫》杂志在线发表了这项成果。

研究人员发现，骨谱系来源的巨噬细胞集落刺激因子-1（Csf-1）能防止发育异常，但对成年后的单细胞生成没有影响。然而，在成年期条件性缺失Csf1会减少单核细胞的存活、分化和迁移，这与它对骨骼发育的影响无关。骨骼组织学显示，单核细胞居住在窦状内皮细胞（EC）和表达瘦素受体（Lepr）的血管周围间质细胞（MSC）附近。靶向敲除窦道内皮细胞的Csf1可选择性地减少Ly6C^-单核细胞，而联合删除内皮细胞和间充质干细胞的Csf1可进一步减少Ly6C^hi细胞。

此外，EC衍生的CSF-1促进了Ly6C^-单核细胞的恢复，并保护小鼠在诱导多菌性败血症后体重下降。因此，单核细胞在血管周围的BM微环境中得到CSF-1不同细胞来源的支持。

据介绍，CSF-1在维持骨髓系细胞方面起着关键作用。然而，CSF-1（Csf1^op/op）的先天性全面缺乏导致严重的肌肉骨骼缺陷，可能间接影响造血功能。

附：英文原文

Title: Colony stimulating factor-1 producing endothelial cells and mesenchymal stromal cells maintain monocytes within a perivascular bone marrow niche

Author: Takuo Emoto, Jessie Lu, Tharini Sivasubramaniyam, Hassaan Maan, Aniqa B. Khan, Amina A. Abow, Stephanie A. Schroer, Sharon J. Hyduk, Marwan G. Althagafi, Trevor D. McKee, Fred Fu, Shiva Shabro, Antigona Ulndreaj, Felix Chiu, Elvira Paneda, Shaun Pacheco, Tao Wang, Angela Li, Jean X. Jiang, Peter Libby, Mansoor Husain, Bo Wang, Barry B. Rubin, Myron I. Cybulsky, Clinton S. Robbins

Issue&Volume: 2022-05-03

Abstract: Macrophage colony stimulating factor-1 (CSF-1) plays a critical role in maintainingmyeloid lineage cells. However, congenital global deficiency of CSF-1 (Csf1op/op) causes severe musculoskeletal defects that may indirectly affect hematopoiesis.Indeed, we show here that osteolineage-derived Csf1 prevented developmental abnormalities but had no effect on monopoiesis in adulthood.However, ubiquitous deletion of Csf1 conditionally in adulthood decreased monocyte survival, differentiation, and migration,independent of its effects on bone development. Bone histology revealed that monocytesreside near sinusoidal endothelial cells (ECs) and leptin receptor (Lepr)-expressing perivascular mesenchymal stromal cells (MSCs). Targeted deletion of Csf1 from sinusoidal ECs selectively reduced Ly6C monocytes, whereas combined depletion of Csf1 from ECs and MSCs further decreased Ly6Chi cells. Moreover, EC-derived CSF-1 facilitated recovery of Ly6C monocytes and protected mice from weight loss following induction of polymicrobialsepsis. Thus, monocytes are supported by distinct cellular sources of CSF-1 withina perivascular BM niche.

DOI: 10.1016/j.immuni.2022.04.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00176-5