[en] 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.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Fievez, Laurence ; Université de Liège - ULiège > Département de sciences fonctionnelles > Biochimie et biologie moléculaire
Desmet, Christophe ; Université de Liège - ULiège > Biochimie et biologie moléculaire
Henry, Emmanuelle; Université Libre de Bruxelles - ULB > Laboratory of Animal Physiology, Institute of Molecular Biology and Medicine
Pajak, Bernard; Université Libre de Bruxelles - ULB > Laboratory of Animal Physiology, Institute of Molecular Biology and Medicine
Hegenbarth, Silke; University of Bonn (Germany) > Institute for Molecular Medicine and Experimental Immunology
Garze, Virginie; Université Libre de Bruxelles - ULB > Laboratory of Animal Physiology, Institute of Molecular Biology and Medicine
Bex, Françoise; Université Libre de Bruxelles - ULB > Laboratory of Microbiology, Institute for Microbiological Research J-M Wiame
Jaspar, Fabrice ; Université de Liège - ULiège > Clinique des grands animaux
Boutet, Philippe
Gillet, Laurent ; Université de Liège - ULiège > Immunologie et vaccinologie
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