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

Natural killer (NK) cells are lymphocytes that are involved in controlling tumors or microbial infections through the production of interferon gamma (IFN-y). Granulocyte colony-stimulating factor (G-CSF) inhibits IFN-y 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-y secretion in NK cells. Specifically, glucocorticoid receptors (GRs) activated by G-CSF inhibit secretion of IFN-y by promoting interactions be-tween SOCS1 promoters and enhancers, as well as increasing the expression of SOCS1. Experiments in mice confirm that G-CSF treatment significantly downregulates IFN-y 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-y by NK cells.

Automated summary

A study found that G-CSF treatment suppresses IFN-y secretion in NK cells. The mechanism involves the activation of GRs, which promote interactions between SOCS1 promoters and enhancers, as well as increasing the expression of SOCS1.