Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK; Cambridge University Hospitals NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge, UK; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Immunity. 2020 Jul 14;53(1):127-142.e7. doi: 10.1016/j.immuni.2020.06.008. Epub 2020 Jun 19.
Located within red pulp cords, splenic red pulp macrophages (RPMs) are constantly exposed to the blood flow, clearing senescent red blood cells (RBCs) and recycling iron from hemoglobin. Here, we studied the mechanisms underlying RPM homeostasis, focusing on the involvement of stromal cells as these cells perform anchoring and nurturing macrophage niche functions in lymph nodes and liver. Microscopy revealed that RPMs are embedded in a reticular meshwork of red pulp fibroblasts characterized by the expression of the transcription factor Wilms' Tumor 1 (WT1) and colony stimulating factor 1 (CSF1). Conditional deletion of Csf1 in WT1 red pulp fibroblasts, but not white pulp fibroblasts, drastically altered the RPM network without altering circulating CSF1 levels. Upon RPM depletion, red pulp fibroblasts transiently produced the monocyte chemoattractants CCL2 and CCL7, thereby contributing to the replenishment of the RPM network. Thus, red pulp fibroblasts anchor and nurture RPM, a function likely conserved in humans.
位于红髓索内的脾脏红髓巨噬细胞（RPMs）不断暴露于血流中，清除衰老的红细胞（RBCs）并从血红蛋白中回收铁。在这里，我们研究了 RPM 稳态的机制，重点关注基质细胞的参与，因为这些细胞在淋巴结和肝脏中执行锚定和滋养巨噬细胞生态位的功能。显微镜观察显示，RPMs 嵌入红髓成纤维细胞的网状结构中，其特征是转录因子 Wilms 瘤 1（WT1）和集落刺激因子 1（CSF1）的表达。WT1 红髓成纤维细胞而非白髓成纤维细胞中条件性缺失 Csf1 会严重改变 RPM 网络，而不会改变循环 CSF1 水平。在 RPM 耗竭时，红髓成纤维细胞短暂产生单核细胞趋化因子 CCL2 和 CCL7，从而有助于 RPM 网络的补充。因此，红髓成纤维细胞锚定并滋养 RPM，这一功能可能在人类中保守。
