SOCS3 Is a Physiological Negative Regulator for Granulopoiesis and Granulocyte Colony-stimulating Factor Receptor Signaling

Akiko Kimura, Ichiko Kinjyo, Yumiko Matsumura, Hiroyuki Mori, Ryuichi Mashima, Mine Harada, Kenneth R. Chien, Hideo Yasukawa, Akihiko Yoshimura

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

The suppressor of cytokine signaling-3 (SOCS3/CIS3) has been shown to be an important negative regulator of cytokines, especially cytokines that activate STAT3. To examine the role of SOCS3 in neutrophils and the granulocyte colony-stimulating factor (G-CSF) signaling in vivo, we compared neutrophils from two types of conditional knockout mice, LysM-Cre:SOCS3fl/fl mice and Tie2-Cre:SOCS3fl/fl mice, in which the Socs3 gene had been deleted in mature neutrophils and hematopoietic stem cells, respectively. The size of the G-CSF-dependent colonies from Tie2-Cre:SOCS3fl/fl mouse bone marrow was much larger than that of colonies from control wild-type mice, while the size of interleukin-3-dependent colonies was similar. Moreover, LysM-Cre:SOCS3fl/fl mice had more neutrophils than SOCS3 fl/fl mice, suggesting that SOCS3 is a negative regulator of G-CSF signaling in neutrophils. Consistent with this notion, G-CSF-induced STAT3 as well as mitogen-activated protein kinase activation was much stronger and prolonged in SOCS3-deficient mature neutrophils than in wildtype neutrophils. The preventive effect of G-CSF on apoptosis was more prominent in SOCS3-deficient mature neutrophils than in control neutrophils. These data indicate that SOCS3 negatively regulates granulopoiesis and G-CSF signaling in neutrophils and may contribute to neutrophilia or neutropenia.

Original languageEnglish
Pages (from-to)6905-6910
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number8
DOIs
Publication statusPublished - 2004 Feb 20
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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