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Cited by 198Cytokine Signaling Pathways and InteractionsBlood disorders and treatmentsChemokine receptors and signaling

STAT3 governs distinct pathways in emergency granulopoiesis and mature neutrophils

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Panopoulos, A. D., Zhang, L., Snow, J. W., Jones, D. M., Smith, A. M., El Kasmi, K. C., Liu, F., Goldsmith, M. A. +3 more·2006·Blood
DOI 10.1182/blood-2006-02-003012PMC PMC1895456
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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.

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  • AD-HIES primary immune defects include intrinsic impairments in neutrophil chemotaxis.

    “intrinsic impairments in neutrophil chemotaxis”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Panopoulos et al., 2006

    The Results (page not provided) show a cell-autonomous chemotaxis defect in STAT3-deficient mouse neutrophils, specifically in responses to the CXCR2 ligands MIP-2 and KC; migration toward fMLP was similar to controls. The paper does not establish that impaired neutrophil chemotaxis is a primary immune defect in people with AD-HIES. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • STAT3 activation mediates neutrophil mobilization in the bone marrow, neutrophil release into the circulation, and neutrophil chemotaxis by upregulating CXCR2/Il8rb and MIP-2/Cxcl2.

    “STAT3 activation mediates neutrophil mobilization in the bone marrow”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Panopoulos et al., 2006

    The Results and Discussion support a role for STAT3 in acute G-CSF–induced neutrophil mobilization from bone marrow into circulation and in chemotaxis toward MIP-2. They do not support the quoted mechanism of upregulating CXCR2/Il8rb and MIP-2/Cxcl2: the Results explicitly state that CXCR2 expression is independent of STAT3 and describe MIP-2 as a chemoattractant used to test the response. The Discussion also cautions that STAT3 is not necessary for all neutrophil mobilization. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
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.
Affiliations
Boston Children's Hospital (US)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2006-12-01
Volume
108
Issue
12
Pages
3682-3690
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2006-02-003012
PMC
PMC1895456
OpenAlex
W2030726748
Cited by
198
References
2
Citations by year
2026: 6 · 2025: 10 · 2024: 6 · 2023: 11 · 2022: 9 · 2021: 11 · 2020: 8 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 10 · 2015: 6 · 2014: 10 · 2013: 13 · 2012: 7
FWCI
6.09
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (R01CA077447, T32CA009598, CA77447, T32 CA09598-16)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Keywords
STAT3, emergency granulopoiesis, neutrophils, granulocyte colony-stimulating factor, G-CSF receptor, JAK/STAT signaling, neutrophil mobilization, neutrophil chemotaxis, CXCR2, actin polymerization, SOCS3, innate immunity, bone marrow
MeSH terms
Suppressor of Cytokine Signaling 3 Protein, Animals, Bacterial Infections, Bone Marrow, Cell Differentiation, Chemotaxis, Immunity, Innate, Neutrophils, Signal Transduction, Granulocyte Colony-Stimulating Factor, Receptors, Granulocyte Colony-Stimulating Factor, Mice, Knockout, Myelopoiesis, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice

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