# Oncostatin M is dispensable for the regulation of hematopoietic stem/progenitor cell traffic by neutrophils

## TL;DR

The study finds that Oncostatin M (OSM) is not essential for neutrophil regulation of hematopoietic stem/progenitor cell movement in the bone marrow.

## Contribution

The research reveals that OSM-independent pathways are primarily responsible for neutrophil regulation of hematopoietic stem/progenitor cell traffic.

## Key findings

- OSM is highly expressed by senescent neutrophils but is not required for modulating hematopoietic stem/progenitor cell levels.
- Neutrophil depletion mobilizes hematopoietic stem/progenitor cells independently of OSM and the CXCL12/CXCR4 axis.
- Macrophage depletion-induced hematopoietic stem/progenitor cell egress depends on OSM.

## Abstract

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 Osm−/− 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.

•OSM is highly expressed and released by activated neutrophils, especially if senescent•Loss of OSM persistently elevated blood HSPCs without affecting neutrophil kinetics•OSM secretion from neutrophils does not regulate HSPCs kinetics in/out their niche•Neutrophil depletion mobilizes HSPCs independently from OSM and CXCL12/CXCR4

OSM is highly expressed and released by activated neutrophils, especially if senescent

Loss of OSM persistently elevated blood HSPCs without affecting neutrophil kinetics

OSM secretion from neutrophils does not regulate HSPCs kinetics in/out their niche

Neutrophil depletion mobilizes HSPCs independently from OSM and CXCL12/CXCR4

Immunology; Components of the immune system