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High levels of circulating GM-CSF^(+) CD4^(+) T cells are predictive of poor outcomes in sepsis patients: a prospective cohort study

查看全文 作  者:Huihuang [1]Huang;Siyu [1]Wang;Tianjun [1]Jiang;Rong [1]Fan;Zheng [2]Zhang;Jinsong [3]Mu;Ke [3]Li;Yonggang [3]Wang;Lei [1]Jin;Fang [3]Lin;Jie [4]Xia;Lijian [3]Sun;Biao [3]Xu;Chengcheng [3]Ji;Jing [5]Chen;Juan [6]Chang;Bo [1]Tu;Bing [1]Song;Chao [1]Zhang;Fu-Sheng [1]Wang;Ruonan [1]Xu 高影响力作者 机构地区:[1]Treatment and Research Center for Infectious Disease,Beijing 302 Hospital,Beijing,China;[2]Clinical Research and Management Center,Beijing 302 Hospital,Beijing,China;[3]Intensive Care Center,Beijing 302 Hospital,Beijing,China;[4]Treatment and Research Center for Liver Failure,Beijing 302 Hospital,Beijing,China;[5]Department of Infectious Diseases,The Affiliated Southwest Hospital of the Third Military Medical University,Chongqing,China;[6]Medical Department,Army General Hospital of PLA,Beijing,China高影响力机构 出  处:《Cellular & Molecular Immunology》索引2019年第16卷第6期,共9页高影响力期刊 基  金:supported by the National Natural Science Foundation of China[grant number 81400626];the National Natural Science Foundation for innovation group[grant number 81721002]. 摘  要:Granulocyte colony-stimulating factor(GM-CSF),produced by CD4^(+)T cells,has recently been implicated in the pathogenesis of inflammatory diseases,such as multiple sclerosis and juvenile arthritis.However,the role of GM-CSF-producing CD4^(+)T cells in sepsis remains unknown.This study reports peripheral changes in GM-CSF-producing CD4^(+)T cells in septic patients and the possible underlying mechanism by which GM-CSF influences the outcome of sepsis.Forty-three septic patients,20 SIRS patients,and 20 healthy controls were enrolled in this study and followed for 28 days to assess mortality.We measured the peripheral frequency of GM-CSF^(+)CD4^(+)T cells and recorded their associated relationship with disease progression.Our data demonstrated that peripheral GM-CSF-producing CD4^(+)T cells were significantly higher in septic patients than in both SIRS patients and healthy controls.These cells exhibit a memory phenotype and impaired IFN-γ-secreting capacity in sepsis patients.Using a receiver operating curve analysis with 8.01%as a cut-off point,the percentage of GM-CSF^(+)CD4^(+)T cells could predict the outcome of septic patients.Combined with the increase in GM-CSF-producing CD4^(+)T cells,inflammatory cytokines IL-1βand IL-6 were also upregulated.Using an in vitro neutrophil model,we found that GM-CSF inhibited C3aR expression,while inducing IL-8 production.Furthermore,this effect was transferrable in plasma from sepsis patients and was attenuated by inhibition of GM-CSF using an anti-GM-CSF antibody.These results indicate that GM-CSF-producing CD4^(+)T cells may serve as a marker of sepsis severity.Thus,targeting GM-CSF overproduction may benefit sepsis patients. 关 键 词:GM-CSF CD4^(+)T cells SEPSIS SIRS
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