STAT3 governs distinct pathways in emergency granulopoiesis and mature neutrophils.

Abstract:

:Granulocyte colony-stimulating factor (G-CSF) is essential for the host response to bacterial infection by controlling neutrophil production in the bone marrow. The G-CSF receptor (G-CSFR) activates the Jak/STAT pathway, although little is understood about how these signals regulate basal and stress-induced granulopoiesis. We examined STAT3 function in granulocytes using a bone marrow conditional knockout mouse model. Our results show that STAT3 has a crucial role in emergency granulopoiesis and mature neutrophil function. STAT3-deficient mice have an aberrant response to G-CSF in vivo, characterized by failure to accumulate immature granulocytes and an increased ratio of mature to immature neutrophils in the bone marrow, peripheral blood, and spleen. Acute neutrophil mobilization is impaired in STAT3-deficient mice as judged by their failure to up-regulate circulating neutrophils following short-term G-CSF exposure. STAT3 also controls neutrophil chemotactic responses to natural ligands for CXCR2 and regulates the magnitude of chemoattractant-induced actin polymerization. These functions of STAT3 are independent of its principal target gene Socs3, which encodes a crucial feedback inhibitor of cytokine signaling. Our results demonstrate the existence of distinct STAT3 target pathways in neutrophils required for granulopoiesis and innate immunity.

journal_name

Blood

journal_title

Blood

authors

Panopoulos AD,Zhang L,Snow JW,Jones DM,Smith AM,El Kasmi KC,Liu F,Goldsmith MA,Link DC,Murray PJ,Watowich SS

doi

10.1182/blood-2006-02-003012

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

3682-90

issue

12

eissn

0006-4971

issn

1528-0020

pii

blood-2006-02-003012

journal_volume

108

pub_type

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