Distinct neutrophil populations arise during certain pathological conditions.The generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain un...Distinct neutrophil populations arise during certain pathological conditions.The generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain unclear.In this study,using an experimental sepsis model that features immunosuppression,we identified a novel population of pathogenic CD200R^(high) neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T(T_(reg))cells.Compared to their CD200R^(low)counterparts,sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction,with reduced chemotactic migration,superoxide anion production,and TNF-αproduction.Increased soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis,and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200R^(high) neutrophils.The administration of anα-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge,leading to increased survival.Transcriptome analysis revealed that CD200R^(high) neutrophils expressed high levels of Igf1,which elicits the generation of Treg cells,while the administration of anα-CD200R antibody inhibited Treg cell generation in a secondary infection model.Taken together,our findings revealed a novel CD200R^(high) neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells.展开更多
目的探讨脑卒中相关肺炎(SAP)外周血CD200/CD200R1通路及CD147表达对病情评估及患者预后的价值.方法选择2017年12月-2019年12月南方医科大学珠江医院急诊科收治的脑卒中急性缺血性脑卒中患者140例作为研究对象,根据其住院期间是否发生...目的探讨脑卒中相关肺炎(SAP)外周血CD200/CD200R1通路及CD147表达对病情评估及患者预后的价值.方法选择2017年12月-2019年12月南方医科大学珠江医院急诊科收治的脑卒中急性缺血性脑卒中患者140例作为研究对象,根据其住院期间是否发生肺部感染分为SAP组(n=55)及非SAP组(n=85),选择同期急诊科收治的因外伤、车祸等入院的患者60例作为对照组.S A P组根据格拉斯哥评分及肺部感染评分进一步分为轻度、中度、重度昏迷组及轻度、中度、重度感染组.采用流式细胞术检测所有患者外周血中CD200、CD200R1水平,采用酶联免疫吸附法检测血清CD147水平.结果SAP组CD200、CD200R1水平低于非SAP组及对照组,CD147高于非SAP组及对照组(P<0.05);非SAP组CD200、CD200R1水平低于对照组,CD147高于对照组;随昏迷程度增加,CD200、CD200R1水平逐渐降低,CD147水平逐渐升高,比较差异具有统计学意义(P<0.05);随感染程度的增加,CD200、CD200R1水平逐渐降低,CD147水平逐渐升高,比较差异具有统计学意义(P<0.05).结论随着脑卒中相关肺炎病情的加重,外周血中CD200、CD200R1水平不断降低,CD147水平不断增加,三指标对于患者预后具有一定的预测价值.展开更多
基金supported by Basic Science Research Program(NRF-2020M3A9D3038435,NRF-2017R1A5A1014560)the Korea Initiative for Fostering the University of Research and Innovation Program(NRF-2020M3H1A1077095)+1 种基金through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT and Future Planning and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(grant number:HI22C2004).
文摘Distinct neutrophil populations arise during certain pathological conditions.The generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain unclear.In this study,using an experimental sepsis model that features immunosuppression,we identified a novel population of pathogenic CD200R^(high) neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T(T_(reg))cells.Compared to their CD200R^(low)counterparts,sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction,with reduced chemotactic migration,superoxide anion production,and TNF-αproduction.Increased soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis,and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200R^(high) neutrophils.The administration of anα-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge,leading to increased survival.Transcriptome analysis revealed that CD200R^(high) neutrophils expressed high levels of Igf1,which elicits the generation of Treg cells,while the administration of anα-CD200R antibody inhibited Treg cell generation in a secondary infection model.Taken together,our findings revealed a novel CD200R^(high) neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells.
文摘目的探讨脑卒中相关肺炎(SAP)外周血CD200/CD200R1通路及CD147表达对病情评估及患者预后的价值.方法选择2017年12月-2019年12月南方医科大学珠江医院急诊科收治的脑卒中急性缺血性脑卒中患者140例作为研究对象,根据其住院期间是否发生肺部感染分为SAP组(n=55)及非SAP组(n=85),选择同期急诊科收治的因外伤、车祸等入院的患者60例作为对照组.S A P组根据格拉斯哥评分及肺部感染评分进一步分为轻度、中度、重度昏迷组及轻度、中度、重度感染组.采用流式细胞术检测所有患者外周血中CD200、CD200R1水平,采用酶联免疫吸附法检测血清CD147水平.结果SAP组CD200、CD200R1水平低于非SAP组及对照组,CD147高于非SAP组及对照组(P<0.05);非SAP组CD200、CD200R1水平低于对照组,CD147高于对照组;随昏迷程度增加,CD200、CD200R1水平逐渐降低,CD147水平逐渐升高,比较差异具有统计学意义(P<0.05);随感染程度的增加,CD200、CD200R1水平逐渐降低,CD147水平逐渐升高,比较差异具有统计学意义(P<0.05).结论随着脑卒中相关肺炎病情的加重,外周血中CD200、CD200R1水平不断降低,CD147水平不断增加,三指标对于患者预后具有一定的预测价值.
