LPG 18：0是哮喘的一般生物标志物，可抑制调节性T细胞的分化和功能
2024/08/28
摘要
背景：哮喘的诊断、严重程度评估和治疗策略的制定是疾病管理的关键方面。由于生物标志物是疾病管理的可靠工具，我们旨在识别和探索与哮喘相关的生物标志物，并研究其机制。
方法：脂质组学用于分析哮喘患者和对照组的血清甘油磷脂。溶血磷脂酰甘油（LPG）的绝对浓度18：0在各种哮喘亚型中进行了定量。小鼠哮喘模型用于确认其作为生物标志物的潜力，并研究其在体内的机制。通过流式细胞术在体外评估 LPG 18：0 对 CD4（+）T细胞分化、增殖和凋亡的影响，同时通过线粒体膜电位、活性氧和ATP产生测量评估线粒体功能障碍。使用小分子抑制剂研究了LPG 18：0 在Tregs中的细胞内机制。
结果：哮喘患者和对照组血清甘油磷脂水平存在差异，哮喘患者LPG 18：0水平明显较高，与哮喘严重程度和对照水平相关。体内和体外研究表明，LPG18：0 损害了幼稚 CD4（+） T细胞分化为Tregs 并损害了其抑制功能。进一步研究表明，LPG18：0处理在Treg分化过程中通过SIRT1介导的去乙酰化降低了FOXP3蛋白水平。
结论：这项研究发现，哮喘患者的血清LPG 18：0水平通常会升高，并作为哮喘的生物标志物。LPG 18：0 通过NAD（+）/SIRT1/FOXP3 通路损害Treg功能。我们的研究揭示了 LPG18：0作为哮喘生物标志物的潜力，阐明了其在哮喘诊断和治疗中的作用。
LPG 18:0 is a general biomarker of asthma andinhibits the differentiation and function ofregulatory T cells
Abudureyimujiang, Aili; Yuqing.
Abstrast
Background: The diagnosis, severity assessment, and development of therapeutic strategies for asthma are crucial aspects of disease management. Since biomarkers are reliable tools in disease management, we aimed to identify and explore asthma-associated biomarkers and investigate their mechanisms.
Methods: Lipidomics was used to profile serum glycerophospholipids in asthmatic patients and controls. The absolute concentration of lysophosphatidylglycerol (LPG) 18:0 was quantified in various asthma subtypes. Mouse asthma models were used to confirm its potential as a biomarker and investigate its mechanisms in vivo. The effects of LPG 18:0 on CD4(+) T cell differentiation, proliferation, and apoptosis were assessed in vitro by flow cytometry, while mitochondrial dysfunction was evaluated through mitochondrial membrane potential, reactive oxygen species, and ATP production measurements. The intracellular mechanism of LPG 18:0 in Tregs was investigated using small molecule inhibitors.
Results：The serum glycerophospholipid profile varied between asthmatic patients and control group, with LPG 18:0 levels being notably higher in asthmatic patients, correlating with asthma severity and control level. In vivo and in vitro studies revealed that LPG18:0 impaired naïve CD4(+) T cell differentiation into Tregs and compromised their suppressive function. Further investigation demonstrated that LPG18:0 treatment reduced the FOXP3 protein level via SIRT1-mediated deacetylation during Treg differentiation.
Conclusions: This study identifies that serum levels of LPG 18:0 are generally elevated in asthmatics and serve as a biomarker for asthma. LPG 18:0 impairs Treg function via the NAD(+)/SIRT1/FOXP3 pathway. Our research reveals the potential of LPG18:0 as a biomarker for asthma, elucidating its role in asthma diagnosis and treatment.
背景：哮喘的诊断、严重程度评估和治疗策略的制定是疾病管理的关键方面。由于生物标志物是疾病管理的可靠工具，我们旨在识别和探索与哮喘相关的生物标志物，并研究其机制。
方法：脂质组学用于分析哮喘患者和对照组的血清甘油磷脂。溶血磷脂酰甘油（LPG）的绝对浓度18：0在各种哮喘亚型中进行了定量。小鼠哮喘模型用于确认其作为生物标志物的潜力，并研究其在体内的机制。通过流式细胞术在体外评估 LPG 18：0 对 CD4（+）T细胞分化、增殖和凋亡的影响，同时通过线粒体膜电位、活性氧和ATP产生测量评估线粒体功能障碍。使用小分子抑制剂研究了LPG 18：0 在Tregs中的细胞内机制。
结果：哮喘患者和对照组血清甘油磷脂水平存在差异，哮喘患者LPG 18：0水平明显较高，与哮喘严重程度和对照水平相关。体内和体外研究表明，LPG18：0 损害了幼稚 CD4（+） T细胞分化为Tregs 并损害了其抑制功能。进一步研究表明，LPG18：0处理在Treg分化过程中通过SIRT1介导的去乙酰化降低了FOXP3蛋白水平。
结论：这项研究发现，哮喘患者的血清LPG 18：0水平通常会升高，并作为哮喘的生物标志物。LPG 18：0 通过NAD（+）/SIRT1/FOXP3 通路损害Treg功能。我们的研究揭示了 LPG18：0作为哮喘生物标志物的潜力，阐明了其在哮喘诊断和治疗中的作用。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Eur Respir J 2024 Aug 15;0(0); 10.1183/13993003.01752-2023. IF：12.339)
(Eur Respir J 2024 Aug 15;0(0); 10.1183/13993003.01752-2023. IF：12.339)
LPG 18:0 is a general biomarker of asthma andinhibits the differentiation and function ofregulatory T cells
Abudureyimujiang, Aili; Yuqing.
Abstrast
Background: The diagnosis, severity assessment, and development of therapeutic strategies for asthma are crucial aspects of disease management. Since biomarkers are reliable tools in disease management, we aimed to identify and explore asthma-associated biomarkers and investigate their mechanisms.
Methods: Lipidomics was used to profile serum glycerophospholipids in asthmatic patients and controls. The absolute concentration of lysophosphatidylglycerol (LPG) 18:0 was quantified in various asthma subtypes. Mouse asthma models were used to confirm its potential as a biomarker and investigate its mechanisms in vivo. The effects of LPG 18:0 on CD4(+) T cell differentiation, proliferation, and apoptosis were assessed in vitro by flow cytometry, while mitochondrial dysfunction was evaluated through mitochondrial membrane potential, reactive oxygen species, and ATP production measurements. The intracellular mechanism of LPG 18:0 in Tregs was investigated using small molecule inhibitors.
Results：The serum glycerophospholipid profile varied between asthmatic patients and control group, with LPG 18:0 levels being notably higher in asthmatic patients, correlating with asthma severity and control level. In vivo and in vitro studies revealed that LPG18:0 impaired naïve CD4(+) T cell differentiation into Tregs and compromised their suppressive function. Further investigation demonstrated that LPG18:0 treatment reduced the FOXP3 protein level via SIRT1-mediated deacetylation during Treg differentiation.
Conclusions: This study identifies that serum levels of LPG 18:0 are generally elevated in asthmatics and serve as a biomarker for asthma. LPG 18:0 impairs Treg function via the NAD(+)/SIRT1/FOXP3 pathway. Our research reveals the potential of LPG18:0 as a biomarker for asthma, elucidating its role in asthma diagnosis and treatment.
上一篇：
奥马珠单抗可减少重度哮喘儿童的过敏反应，并允许引入食物治疗:一项观察性研究
下一篇：
与哮喘相比，特应性皮炎度普利尤单抗诱导的眼部不良事件的患病率更高：日常实践分析
