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

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

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: cheng_li@pku.edu.cn.
  • 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: xjhrm@medmail.com.cn.
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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