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Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1α-dependent glycolysis

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Cellular & Molecular Immunology 2018年第6期15卷 618-629页

作者： Yun Lu Huanrong Liu Yujing Bi Hui Yang Yan Li Jian Wang Zhengguo Zhang Yu Wang Chunxiao Li Anna Jia Linian Han Ying Hu Yong Zhao Ruoning Wang Guangwei Liu Department of Immunology School of Basic Medical SciencesFudan UniversityShanghai 200032China Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education Institute of Cell BiologyCollege of Life SciencesBeijing Normal UniversityBeijing 100875China State Key laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Center for Childhood Cancer and Blood Diseases Hematology/Oncology and BMTThe Research Institute at Nationwide Children's HospitalOhio State UniversityColumbusOhio 43205USA

Immunomodulatory signaling imposes tight regulations on metabolic programs within immune cells and consequentially determines immune response *** the glucocorticoid receptor(GR)has been recently implicated in regulating the function of myeloid-derived suppressor cells(MDSCs),whether the dysregulation of GR in MDSCs is involved in immune-mediated hepatic diseases and how GR regulates the function of MDSCs in such a context remains ***,we revealed the dysregulation of GR expression in MDSCs during innate immunological hepatic injury(IMH)and found that GR regulates the function of MDSCs through modulating HIF1α-dependent *** modulation of GR by its agonist(dexamethasone,Dex)protects IMH mice against inflammatory ***,GR signaling suppresses HIF1αand HIF1α-dependent glycolysis in MDSCs and thus promotes the immune suppressive activity of *** studies reveal a role of GR-HIF1αin regulating the metabolism and function of MDSCs and further implicate MDSC GR signaling as a potential therapeutic target in hepatic diseases that are driven by innate immune cell-mediated systemic inflammation.

关键词： glucocorticoid-receptor glycolysis innate immunity liver injuries metabolism myeloid-derived suppressive cells tolerance

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