TY - JOUR
T1 - STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation
AU - Lee, Chien Kuo
AU - Raz, Regina
AU - Gimeno, Ramon
AU - Gertner, Rachel
AU - Wistinghausen, Birte
AU - Takeshita, Kenichi
AU - DePinho, Ronald A.
AU - Levy, David E.
N1 - Funding Information:
We thank Ross Basch for invaluable discussions and advice on CFU assays, Giorgio Inghirami, Alan Frey, Joellen Shaw, and Jack Hessler for helpful discussions, and John Hirst for FACS analysis. We are grateful to Michel Aguet for the gift of Mx-Cre mice. R.A.D. is an American Cancer Society Research Professor. This work was supported by grants from the NIH and the AHA.
PY - 2002
Y1 - 2002
N2 - STAT3 has been described as an essential component of G-CSF-driven cell proliferation and granulopoiesis. This notion was tested by conditional gene ablation in transgenic mice. Contrary to expectation, granulocytes developed from STAT3 null bone marrow progenitors, and STAT3 null neutrophils displayed mature effector functions. Rather than a deficit in granulopoiesis, mice lacking STAT3 in their hematopoietic progenitors developed neutrophilia, and bone marrow cells were hyperresponsive to G-CSF stimulation. These studies provide direct evidence for STAT3-independent granulopoiesis and suggest that STAT3 directs a negative feedback loop necessary for controlling neutrophil numbers, possibly through induced expression of the signaling inhibitor, SOCS3.
AB - STAT3 has been described as an essential component of G-CSF-driven cell proliferation and granulopoiesis. This notion was tested by conditional gene ablation in transgenic mice. Contrary to expectation, granulocytes developed from STAT3 null bone marrow progenitors, and STAT3 null neutrophils displayed mature effector functions. Rather than a deficit in granulopoiesis, mice lacking STAT3 in their hematopoietic progenitors developed neutrophilia, and bone marrow cells were hyperresponsive to G-CSF stimulation. These studies provide direct evidence for STAT3-independent granulopoiesis and suggest that STAT3 directs a negative feedback loop necessary for controlling neutrophil numbers, possibly through induced expression of the signaling inhibitor, SOCS3.
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U2 - 10.1016/S1074-7613(02)00336-9
DO - 10.1016/S1074-7613(02)00336-9
M3 - Article
C2 - 12150892
AN - SCOPUS:0036338213
SN - 1074-7613
VL - 17
SP - 63
EP - 72
JO - Immunity
JF - Immunity
IS - 1
ER -