In vivo G-CSF treatment activates the GR-SOCS1 axis to suppress IFN-γ secretion by natural killer cells

Cell Rep. 2022 Sep 13;40(11):111342. doi: 10.1016/j.celrep.2022.111342.


Natural killer (NK) cells are lymphocytes that are involved in controlling tumors or microbial infections through the production of interferon gamma (IFN-γ). Granulocyte colony-stimulating factor (G-CSF) inhibits IFN-γ secretion by NK cells, but the mechanism underlying this effect remains unclear. Here, by comparing the multi-omics profiles of human NK cells before and after in vivo G-CSF treatment, we identify a pathway that is activated in response to G-CSF treatment, which suppresses IFN-γ secretion in NK cells. Specifically, glucocorticoid receptors (GRs) activated by G-CSF inhibit secretion of IFN-γ by promoting interactions between SOCS1 promoters and enhancers, as well as increasing the expression of SOCS1. Experiments in mice confirm that G-CSF treatment significantly downregulates IFN-γ secretion and upregulates GR and SOCS1 expression in NK cells. In addition, GR blockade by the antagonist RU486 significantly reverses the effects of G-CSF, demonstrating that GRs upregulate SOCS1 and inhibit the production of IFN-γ by NK cells.

Keywords: CP: Immunology; G-CSF; IFN-γ; NK; SOCS1; glucocorticoid receptor; multi-omics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Humans
  • Interferon-gamma* / metabolism
  • Killer Cells, Natural* / metabolism
  • Mice
  • Suppressor of Cytokine Signaling 1 Protein / metabolism
  • Suppressor of Cytokine Signaling Proteins / metabolism


  • SOCS1 protein, human
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Granulocyte Colony-Stimulating Factor
  • Interferon-gamma