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.
Xiangyu Zhao  1 ,  Ting Peng  2 ,  Xunhong Cao  1 ,  Yingping Hou  2 ,  Ruifeng Li  3 ,  Tingting Han  1 ,  Zeying Fan  1 ,  Ming Zhao  1 ,  Yingjun Chang  1 ,  Hebin Chen  4 ,  Cheng Li  5 ,  Xiaojun Huang  6
Affiliations
  • 1. Peking University People's Hospital, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
  • 2. School of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing, China.
  • 3. Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China.
  • 4. Institute of Health Service and Transfusion Medicine, Beijing, China.
  • 5. School of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing, China. Electronic address: [email protected].
  • 6. Peking University People's Hospital, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. Electronic address: [email protected].
PMID: 36103837 DOI: 10.1016/j.celrep.2022.111342
Abstract

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.
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