Related Experiment Video
Updated: Jul 12, 2026

ATAC-Seq Library Preparation of Murine Bone Marrow-Derived Neutrophils
Published on: January 3, 2025
STAT5 is an ambivalent regulator of neutrophil homeostasis
Laurence Fiévez1, Christophe Desmet, Emmanuelle Henry
1Laboratory of Cellular and Molecular Physiology, GIGA-Research, University of Liège, Liège, Belgium.
Background:
Although STAT5 promotes survival of hematopoietic progenitors, STAT5-/- mice develop mild neutrophilia.
Methodology/Principal Findings:
Here, we show that in STAT5-/- mice, liver endothelial cells (LECs) autonomously secrete high amounts of G-CSF, allowing myeloid progenitors to overcompensate for their intrinsic survival defect. However, when injected with pro-inflammatory cytokines, mutant mice cannot further increase neutrophil production, display a severe deficiency in peripheral neutrophil survival, and are therefore unable to maintain neutrophil homeostasis. In wild-type mice, inflammatory stimulation induces rapid STAT5 degradation in LECs, G-CSF production by LECs and other cell types, and then sustained mobilization and expansion of long-lived neutrophils.
Conclusion:
We conclude that STAT5 is an ambivalent factor. In cells of the granulocytic lineage, it exerts an antiapoptotic function that is required for maintenance of neutrophil homeostasis, especially during the inflammatory response. In LECs, STAT5 negatively regulates granulopoiesis by directly or indirectly repressing G-CSF expression. Removal of this STAT5-imposed brake contributes to induction of emergency granulopoiesis.
Insights
Signal transducer and activator of transcription 5 (STAT5) plays a dual role in neutrophil regulation. STAT5 deficiency impairs neutrophil survival during inflammation, while its absence in liver endothelial cells promotes granulopoiesis.
Area of Science:
- Hematology
- Immunology
- Molecular Biology
Background:
- STAT5 is known to promote hematopoietic progenitor survival.
- STAT5-deficient mice exhibit mild neutrophilia, suggesting a complex role in hematopoiesis.
Purpose of the Study:
- To elucidate the role of STAT5 in neutrophil homeostasis and granulopoiesis.
- To investigate the function of STAT5 in liver endothelial cells (LECs) and granulocytic lineage cells.
Main Methods:
- Analysis of STAT5-deficient (STAT5-/-) mice.
- Assessment of G-CSF secretion by LECs.
- Evaluation of neutrophil production and survival under inflammatory conditions.
Main Results:
- STAT5-/- mice show autonomous G-CSF secretion by LECs, compensating for myeloid progenitor defects.
- Mutant mice exhibit impaired neutrophil production and survival upon inflammatory stimulation.
- Wild-type mice demonstrate STAT5 degradation in LECs, leading to G-CSF production and neutrophil mobilization during inflammation.
Conclusions:
- STAT5 has an ambivalent role: promoting granulocytic survival but inhibiting G-CSF expression in LECs.
- STAT5 acts as a negative regulator of granulopoiesis in LECs by repressing G-CSF.
- STAT5 is crucial for maintaining neutrophil homeostasis, particularly during inflammatory responses.
Related Concept Videos
The JAK-STAT Signaling Pathway
Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Regulation of Bacterial Virulence
Other Stress Responses in Bacteria
Regulation of Hematopoietic Stem Cells
Differentiation of Common Myeloid Progenitor Cells
