Socs3 maintains the specificity of biological responses to cytokine signals during granulocyte and macrophage differentiation.

Experimental Hematology
Ben A CrokerAndrew W Roberts

Abstract

Granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) play key roles in regulating emergency granulopoiesis and inflammation, and are both negatively regulated by the inducible intracellular protein suppressor of cytokine signaling-3 (Socs3). Mice with Socs3 deleted specifically in hematopoietic cells succumb to severe neutrophil and macrophage-driven inflammation by 1 year of age, and responses to G-CSF are grossly exacerbated. In order to determine which elements of cellular responses to cytokines require Socs3, we have examined the differentiative and proliferative capacity of hematopoietic progenitor cells stimulated by G-CSF and IL-6. The differentiation of Socs3-deficient progenitor cells is skewed toward macrophage production in response to G-CSF or IL-6, whereas wild-type progenitor cells produce mainly neutrophils. The proliferative capacity of Socs3-deficient progenitor cells is greatly enhanced in response to G-CSF at all concentrations, but only at low concentrations for IL-6. Strikingly, synergistic responses to costimulation with stem cell factor and IL-6 (but not G-CSF) are lost at higher concentrations in Socs3-deficient progenitor cells. Cytokine-induced expression of transcriptional regulators...Continue Reading

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Citations

Apr 27, 2011·Immunology and Cell Biology·Ben A CrokerAndrew W Roberts
Jun 29, 2010·Blood·Huiyuan ZhangStephanie S Watowich
Jan 15, 2014·Seminars in Immunology·Jeffrey J BabonNicos A Nicola
Nov 26, 2008·Pharmacology & Therapeutics·R W ChapmanJ S Fine
May 12, 2012·Growth Factors·Jeffrey J Babon, Nicos A Nicola
Dec 3, 2014·Seminars in Immunology·Martin E Rottenberg, Berit Carow
Dec 17, 2009·Neuron·Patrice D SmithZhigang He
May 18, 2016·Cytokine & Growth Factor Reviews·Emily J HillmerStephanie S Watowich
Mar 30, 2018·Frontiers in Immunology·Shirin HasanAsim Rizvi

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