STAT3 governs distinct pathways in emergency granulopoiesis and mature neutrophils

Athanasia D. Panopoulos, Ling Zhang, Jonathan W. Snow, Daniel M. Jones, Amber M. Smith, Karim C. El Kasmi, Fulu Liu, Mark A. Goldsmith, Daniel C. Link, Peter J. Murray, Stephanie S. Watowich

Research output: Contribution to journalArticle

122 Scopus citations

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 upregulate 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.

Original languageEnglish
Pages (from-to)3682-3690
Number of pages9
JournalBlood
Volume108
Issue number12
DOIs
StatePublished - Dec 1 2006

Fingerprint Dive into the research topics of 'STAT3 governs distinct pathways in emergency granulopoiesis and mature neutrophils'. Together they form a unique fingerprint.

  • Cite this

    Panopoulos, A. D., Zhang, L., Snow, J. W., Jones, D. M., Smith, A. M., El Kasmi, K. C., Liu, F., Goldsmith, M. A., Link, D. C., Murray, P. J., & Watowich, S. S. (2006). STAT3 governs distinct pathways in emergency granulopoiesis and mature neutrophils. Blood, 108(12), 3682-3690. https://doi.org/10.1182/blood-2006-02-003012