AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiati...AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un⁃explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1^(fl/fl))mice and Treg-specific AMPKα1 knockout mice(AMPKα1^(fl/fl)Foxp3^(cre)mice).RESULTS:Compared to AMPKα1^(fl/fl)mice,the percentage of eosinophils in the bone marrow of AMPKα1^(fl/fl)Foxp3^(cre)mice was significant⁃ly reduced.Additionally,while the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice exhibited normal structure,both its size and the ratio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4^(+)T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice compared to AMPKα1^(fl/fl)mice.Importantly,the proportion of Siglec-F+CD11b^(+)eosinophils in the thymus was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4^(+)T cells in peripheral blood,alongside a decrease in the proportion of mature CD8^(+)T cells.Similarly,the proportion of CD4^(+)T cells in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice was elevated compared to AMPKα1^(fl/fl)mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice.In lymph nodes,the medullary boundaries in AMPKα1^(fl/fl)Foxp3^(cre)mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1^(fl/fl)mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3^(+)T cell population,particularly the CD8^(+)T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice,the percentage of CD4^(+)T cells was markedly in⁃creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1^(fl/fl)Foxp3^(cre)and AMPKα1^(fl/fl)mice.CONCLUSION:The populations of mature Tregs,CD8^(+)T cells and eosinophils in various im⁃mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.展开更多
YQ0902孔位于浙江南部瓯江三角洲南侧温瑞平原上。沉积相、粒度分析以及AMS14C测年数据表明,硬土层之下为海洋氧同位素3阶段(MIS 3)形成的潟湖相沉积,据此推测MIS3高海平面至少达到现今海平面之下30m左右(未经构造升降和沉积物压实作用...YQ0902孔位于浙江南部瓯江三角洲南侧温瑞平原上。沉积相、粒度分析以及AMS14C测年数据表明,硬土层之下为海洋氧同位素3阶段(MIS 3)形成的潟湖相沉积,据此推测MIS3高海平面至少达到现今海平面之下30m左右(未经构造升降和沉积物压实作用等影响的校正,下同)。硬土层的成土过程发生于MIS2,其母质部分为MIS3的潟湖沉积,部分为河漫滩沉积。硬土层之上是一套形成于全新世的海侵—海退旋回,与长江三角洲南翼前缘的沉积相组合类似。研究钻孔初始海泛面约形成于9 cal ka BP,推算当时的海平面约低于现今海平面25m。中全新世最大海侵前后,东亚季风较强,通过径流或沿岸流输入本区的沉积物较充足,沉积速率较大。随着海平面相对稳定或略有下降,东亚季风减弱,可容空间减小,中晚全新世(5～2 cal ka BP)沉积速率较低。高分辨率的XRF岩心扫描获得的元素相对含量是古环境与古气候研究的重要指标,其中Cl/Ti、Fe/Ti值可分别作为海相性(与海洋联通程度)与东亚季风强弱的替代指标。展开更多
基金the National Natural Science Foundation of China(62304252)the Youth Innovation Promotion Association of Chinese Academy Sciences(CAS)and IMECAS-HKUST-Joint Laboratory of Microelectronics。
基金Supported by the National Natural Science Foundation of China(No.81800423)the Guangdong Medical Science and Technology Research project(No.B2022102)。
文摘AIM:Regulatory T cells(Tregs)are a specialized subset of CD4^(+)T cells primarily involved in im⁃munosuppressive functions.AMP-activated protein kinase(AMPK)serves as a metabolic sensor that governs the differen⁃tiation,maturation,and immune functions of Tregs through metabolic reprogramming.However,the impact of AMPKα1(the catalytic subunit of AMPK)knockout specifically in Tregs on the host's immune microenvironment remains largely un⁃explored.METHODS:Histological changes in immune organs were assessed using HE staining.The types of immune cells and their relative population percentages in immune organs and blood were quantified through flow cytometry in both AMPKα1flox/flox(AMPKα1^(fl/fl))mice and Treg-specific AMPKα1 knockout mice(AMPKα1^(fl/fl)Foxp3^(cre)mice).RESULTS:Compared to AMPKα1^(fl/fl)mice,the percentage of eosinophils in the bone marrow of AMPKα1^(fl/fl)Foxp3^(cre)mice was significant⁃ly reduced.Additionally,while the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice exhibited normal structure,both its size and the ratio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduction in the total percentage of immature double-negative(DN)cells.Consequently,the percentage of CD4^(+)T cells derived from these DN cells also decreased,even though the percentages of DN1 and DN4 cells were higher in the thymus of AMPKα1^(fl/fl)Foxp3^(cre)mice compared to AMPKα1^(fl/fl)mice.Importantly,the proportion of Siglec-F+CD11b^(+)eosinophils in the thymus was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice.Knockout of AMPKα1 in Tregs resulted in a marked increase in the percentage of CD4^(+)T cells in peripheral blood,alongside a decrease in the proportion of mature CD8^(+)T cells.Similarly,the proportion of CD4^(+)T cells in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice was elevated compared to AMPKα1^(fl/fl)mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1^(fl/fl)Foxp3^(cre)mice.In lymph nodes,the medullary boundaries in AMPKα1^(fl/fl)Foxp3^(cre)mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1^(fl/fl)mice.Furthermore,the knockout of AMPKα1 in Tregs reduced the CD3^(+)T cell population,particularly the CD8^(+)T cell population,in lymph nodes.Although the mature Treg cell population was significantly lower in AMPKα1^(fl/fl)Foxp3^(cre)mice,the percentage of CD4^(+)T cells was markedly in⁃creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1^(fl/fl)Foxp3^(cre)and AMPKα1^(fl/fl)mice.CONCLUSION:The populations of mature Tregs,CD8^(+)T cells and eosinophils in various im⁃mune organs were significantly altered in mice with Treg-specific AMPKα1 knockout,suggesting a potential remodeling of the host immune microenvironment in response to inflammatory stimuli.
文摘YQ0902孔位于浙江南部瓯江三角洲南侧温瑞平原上。沉积相、粒度分析以及AMS14C测年数据表明,硬土层之下为海洋氧同位素3阶段(MIS 3)形成的潟湖相沉积,据此推测MIS3高海平面至少达到现今海平面之下30m左右(未经构造升降和沉积物压实作用等影响的校正,下同)。硬土层的成土过程发生于MIS2,其母质部分为MIS3的潟湖沉积,部分为河漫滩沉积。硬土层之上是一套形成于全新世的海侵—海退旋回,与长江三角洲南翼前缘的沉积相组合类似。研究钻孔初始海泛面约形成于9 cal ka BP,推算当时的海平面约低于现今海平面25m。中全新世最大海侵前后,东亚季风较强,通过径流或沿岸流输入本区的沉积物较充足,沉积速率较大。随着海平面相对稳定或略有下降,东亚季风减弱,可容空间减小,中晚全新世(5～2 cal ka BP)沉积速率较低。高分辨率的XRF岩心扫描获得的元素相对含量是古环境与古气候研究的重要指标,其中Cl/Ti、Fe/Ti值可分别作为海相性(与海洋联通程度)与东亚季风强弱的替代指标。
