title: STAT5 is an ambivalent regulator of neutrophil homeostasis.
abstract: 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.
authors: Laboratory of Cellular and Molecular Physiology, GIGA-Research, University of Liège, Liège, Belgium.
authors: Laurence
authors: L
authors: Fiévez
authors: Christophe
authors: C
authors: Desmet
authors: Emmanuelle
authors: E
authors: Henry
authors: Bernard
authors: B
authors: Pajak
authors: Silke
authors: S
authors: Hegenbarth
authors: Virginie
authors: V
authors: Garzé
authors: Françoise
authors: F
authors: Bex
authors: Fabrice
authors: F
authors: Jaspar
authors: Philippe
authors: P
authors: Boutet
authors: Laurent
authors: L
authors: Gillet
authors: Alain
authors: A
authors: Vanderplasschen
authors: Percy A
authors: PA
authors: Knolle
authors: Oberdan
authors: O
authors: Leo
authors: Muriel
authors: M
authors: Moser
authors: Pierre
authors: P
authors: Lekeux
authors: Fabrice
authors: F
authors: Bureau
mesh_terms: 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
chemical_list: D016207:Cytokines; D050799:STAT5 Transcription Factor; D016179:Granulocyte Colony-Stimulating Factor
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