Rodella Anna, Boscaro Carlotta, Amendolagine Francesco Ivan, Migliozzi Ludovica, Molon Barbara, Viola Antonella, Albiero Mattia, Fadini Gian Paolo
Veneto Institute of Molecular Medicine, 35100 Padova, Padua, Italy.
Department of Medicine, University of Padova, 35100 Padova, Padua, Italy.
iScience. 2025 May 12;28(6):112646. doi: 10.1016/j.isci.2025.112646. eCollection 2025 Jun 20.
Hematopoietic stem/progenitor cell (HSPC) trafficking in and out of the bone marrow (BM) is essential for immune surveillance and hematopoietic balance. We previously identified Oncostatin M (OSM), primarily from myeloid cells, as a key regulator of HSPC traffic. Here, we show that neutrophils highly express and secrete OSM, especially when senesced. However, OSM is not required for neutrophil-mediated modulation of steady-state or circadian HSPC levels. Aged neutrophils returning to the BM reduce HSPC levels in peripheral blood (PB) independently of OSM, suggesting additional mechanisms beyond CXCL12/CXCR4 axis. While neutrophil transfer modulated HSPC kinetics in wild-type mice, OSM-secreting neutrophils failed to normalize elevated PB-HSPC levels in mice, though recombinant OSM successfully did. Macrophage depletion-induced HSPC egress was OSM-dependent, but neutrophil depletion elevated PB-HSPCs regardless of OSM. These findings reveal that neutrophils regulate HSPC migration via largely OSM-independent pathways, emphasizing the importance of cell-specific and context-dependent cues within the BM niche.
造血干/祖细胞（HSPC）进出骨髓（BM）对于免疫监视和造血平衡至关重要。我们之前鉴定出主要来自髓系细胞的抑瘤素M（OSM）是HSPC转运的关键调节因子。在此，我们表明中性粒细胞高度表达并分泌OSM，尤其是在衰老时。然而，中性粒细胞介导的稳态或昼夜HSPC水平调节并不需要OSM。返回骨髓的衰老中性粒细胞独立于OSM降低外周血（PB）中的HSPC水平，提示除CXCL12/CXCR4轴之外的其他机制。虽然中性粒细胞转移调节野生型小鼠中的HSPC动力学，但分泌OSM的中性粒细胞未能使小鼠中升高的PB-HSPC水平恢复正常，尽管重组OSM成功做到了这一点。巨噬细胞耗竭诱导的HSPC流出是OSM依赖性的，但中性粒细胞耗竭无论OSM如何都会升高PB-HSPCs。这些发现揭示中性粒细胞通过很大程度上不依赖OSM的途径调节HSPC迁移，强调了骨髓微环境中细胞特异性和背景依赖性线索的重要性。
