STAT5 is an ambivalent regulator of neutrophil homeostasis.
BACKGROUND
Although STAT5 promotes survival of hematopoietic progenitors, STAT5-/- mice develop mild neutrophilia.


RESULTS
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.


CONCLUSIONS
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.
Fiévez
Laurence
L
Laboratory of Cellular and Molecular Physiology, GIGA-Research, University of Liège, Liège, Belgium.
Desmet
Christophe
C
Henry
Emmanuelle
E
Pajak
Bernard
B
Hegenbarth
Silke
S
Garzé
Virginie
V
Bex
Françoise
F
Jaspar
Fabrice
F
Boutet
Philippe
P
Gillet
Laurent
L
Vanderplasschen
Alain
A
Knolle
Percy A
PA
Leo
Oberdan
O
Moser
Muriel
M
Lekeux
Pierre
P
Bureau
Fabrice
F
D000818:Animals; D019070:Cell Lineage; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology / Q000502:physiology; D006706:Homeostasis; D007249:Inflammation / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
D016207:Cytokines; D050799:STAT5 Transcription Factor; D016179:Granulocyte Colony-Stimulating Factor
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