中国病理生理杂志2025，Vol.41Issue(6)：1041-1054,14.DOI:10.3969/j.issn.1000-4718.2025.06.001
Treg特异性AMPKα1缺失改变小鼠免疫器官中免疫细胞的组成
Treg-specific AMPKα1 deficiency alters immune cell compositions in immune organs of mice
摘要
Abstract
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(AMPKα1fl/fl)mice and Treg-specific AMPKα1 knockout mice(AMPKα1fl/flFoxp3cre mice).RESULTS:Compared to AMPKα1fl/fl mice,the percentage of eosinophils in the bone marrow of AMPKα1fl/flFoxp3cre mice was significant-ly reduced.Additionally,while the thymus of AMPKα1fl/flFoxp3cre mice exhibited normal structure,both its size and the ra-tio of thymus weight to body weight were significantly decreased.The knockout of AMPKα1 in Tregs led to a notable reduc-tion 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 AMPKα1fl/flFoxp3cre mice compared to AMPKα1fl/fl mice.Importantly,the proportion of Siglec-F+CD11b+eosinophils in the thymus was significantly lower in AMPKα1fl/flFoxp3cre 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.Similar-ly,the proportion of CD4+T cells in the spleen of AMPKα1fl/flFoxp3cre mice was elevated compared to AMPKα1fl/fl mice.In contrast,the proportion of neutrophils significantly decreased,while mononuclear cell proportions increased in the spleen of AMPKα1fl/flFoxp3cre mice.In lymph nodes,the medullary boundaries in AMPKα1fl/flFoxp3cre mice were blurred,and the lymphoid follicles were missing,a feature not observed in AMPKα1fl/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 AMPKα1fl/flFoxp3cre mice,the percentage of CD4+T cells was markedly in-creased.In contrast,there was no statistically significant difference in granulocyte populations between AMPKα1fl/flFoxp3cre and AMPKα1fl/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.关键词
AMP活化蛋白激酶α1/调节性T细胞/叉头框蛋白P3/嗜酸性粒细胞/免疫微环境Key words
AMP-activated protein kinase α1/regulatory T cells/forkhead box P3/eosinophils/immune mi-croenvironment分类
基础医学引用本文复制引用
阮璋,杨文静,于天力,李拼贤,张舜辉,林彩霞,郑凌云,王丽京..Treg特异性AMPKα1缺失改变小鼠免疫器官中免疫细胞的组成[J].中国病理生理杂志,2025,41(6):1041-1054,14.基金项目
Supported by the National Natural Science Foundation of China(No.81800423),and the Guangdong Medical Science and Technology Research project(No.B2022102) （No.81800423）
