The Ratio of Regulatory (FOXP3+) to Total (CD3+) T Cells Determined by Epigenetic Cell Counting and Cardiovascular Disease Risk: A Prospective Case-cohort Study in Non-diabetics.
The Ratio of Regulatory (FOXP3+) to Total (CD3+) T Cells Determined by Epigenetic Cell Counting and Cardiovascular Disease Risk: A Prospective Case-cohort Study in Non-diabetics.
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DOI：
10.1016/j.ebiom.2016.07.035
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发表时间：
2016-09
期刊：
影响因子：
11.1
通讯作者：
Kuehn, Tilman
中科院分区：
文献类型：
--
作者：
Barth, Sebastian Dietmar;Kaaks, Rudolf;Johnson, Theron;Katzke, Verena;Gellhaus, Katharina;Schulze, Janika Josephin;Olek, Sven;Kuehn, Tilman
关键词：
实验和临床证据表明，动脉粥样硬化中的炎症过程和心血管并发症的发展是由调节性T细胞（Treg）介导的对斑块抗原的免疫耐受的丧失所促进的。然而，全身Treg频率的改变与心血管疾病发病率之间的关系仍不确定。欧洲癌症与营养前瞻性调查(EPIC)-Heidelberg进行了一项嵌套病例队列研究，包括随机亚队列（n = 778）和原发性心肌梗死（n = 276）和缺血性中风（n = 151）。通过基于表观遗传学的实时定量pcr辅助细胞计数，检测诊断前血液中FOXP3 + Treg和总CD3 + t淋巴细胞（tTL）频率。多变量、prentice加权Cox回归分析显示，较低的Treg/tTL比率与心肌梗死（最低与最高的性别特异性四分位数；风险比：0.72,95%可信区间：0.46至1.13;Ptrend = 0.51）或中风（HR: 0.90, 95% CI: 0.51至1.60;Ptrend = 0.78）的风险无关。Treg/tTL比值与c反应蛋白、HbA1c和各种脂质参数无相关性。在普通人群中的中年人中，总T细胞室中Tregs相对频率的不平衡并不会增加心肌梗死或中风的风险。我们研究了通过调节（FOXP3+）对总（CD3+） T细胞反映的外周免疫耐受是否与心血管疾病风险有关。基于表观遗传学，qPCR辅助细胞计数用于定量长期储存的灰褐色被样品中的T细胞亚群。treg介导的免疫耐受降低并不会增加主要心血管事件的风险。动脉内膜炎症在动脉粥样硬化性心血管疾病中起核心作用，并可能由于针对斑块抗原的自身免疫样反应而发展。虽然调节性T细胞（Tregs）和效应T细胞之间的比例被认为控制着这种免疫反应结果和T细胞室内的耐受性，但我们发现与主要CVD事件的发生率没有关联。这些发现表明，在CVD患者中观察到的全身Treg频率降低是在疾病表现之后而不是之前出现的，并且Treg在生理范围内的变化可能不像以前报道的那样构成CVD的易感危险因素。
Experimental and clinical evidence indicate that inflammatory processes in atherogenesis and the development of cardiovascular complications are promoted by a loss of regulatory T cell (Treg)-mediated immunological tolerance to plaque antigens. Yet, the association between alterations of systemic Treg frequency and cardiovascular disease incidence remains uncertain. A nested case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg, comprising a random subcohort (n = 778) and primary cases of myocardial infarction (MI, n = 276) and ischemic stroke (n = 151). Pre-diagnostic FOXP3 + Treg and total CD3 + T-lymphocyte (tTL) frequencies in blood were measured by epigenetic-based, quantitative real-time PCR-assisted cell counting. Multivariate, Prentice-weighted Cox regression analyses revealed that lower Treg/tTL ratios were not associated with the risk of either MI (lowest vs. highest sex-specific quartile; hazard ratio: 0.72, 95% confidence interval: 0.46 to 1.13; Ptrend = 0.51) or stroke (HR: 0.90, 95% CI: 0.51 to 1.60; Ptrend = 0.78). There were no correlations of Treg/tTL ratios with C-reactive protein, HbA1c, and various lipid parameters. Among middle-aged adults from the general population, imbalances in the relative frequency of Tregs within the total T cell compartment do not confer an increased risk of MI or stroke. We studied if peripheral immune tolerance, as reflected by regulatory (FOXP3+) to total (CD3+) T cells, relates to CVD risk. Epigenetic-based, qPCR assisted cell counting was used to quantify T cell subsets in long-term stored buffy coat samples. Lower Treg-mediated immune tolerance does not confer an increased risk of major CVD events. Inflammation in the arterial intima plays a central role in atherosclerotic cardiovascular disease and may develop owing to autoimmune-like responses targeted against plaque antigens. While the ratio between regulatory T cells (Tregs) and effector T cells is thought to control such immune response outcomes and tolerance within the T cell compartment, we found no association with incidence of major CVD events. These findings imply that reduced systemic Treg frequencies observed in CVD patients follow rather than precede disease manifestation and that Treg variation within a physiological range may not – as previously reported - constitute a pre-disposing risk factor for CVD.
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影响因子：
20.1
作者：
Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
8.2
作者：
Langenberg, C.;Sharp, S.;Forouhi, N. G.;Franks, P. W.;Schulze, M. B.;Kerrison, N.;Ekelund, U.;Barroso, I.;Panico, S.;Tormo, M. J.;Spranger, J.;Griffin, S.;van der Schouw, Y. T.;Amiano, P.;Ardanaz, E.;Arriola, L.;Balkau, B.;Barricarte, A.;Beulens, J. W. J.;Boeing, H.;Bueno-de-Mesquita, H. B.;Buijsse, B.;Chirlaque Lopez, M. D.;Clavel-Chapelon, F.;Crowe, F. L.;de Lauzon-Guillan, B.;Deloukas, P.;Dorronsoro, M.;Drogan, D.;Froguel, P.;Gonzalez, C.;Grioni, S.;Groop, L.;Groves, C.;Hainaut, P.;Halkjaer, J.;Hallmans, G.;Hansen, T.;Huerta Castano, J. M.;Kaaks, R.;Key, T. J.;Khaw, K. T.;Koulman, A.;Mattiello, A.;Navarro, C.;Nilsson, P.;Norat, T.;Overvad, K.;Palla, L.;Palli, D.;Pedersen, O.;Peeters, P. H.;Quiros, J. R.;Ramachandran, A.;Rodriguez-Suarez, L.;Rolandsson, O.;Romaguera, D.;Romieu, I.;Sacerdote, C.;Sanchez, M. J.;Sandbaek, A.;Slimani, N.;Sluijs, I.;Spijkerman, A. M. W.;Teucher, B.;Tjonneland, A.;Tumino, R.;van der A, D. L.;Verschuren, W. M. M.;Tuomilehto, J.;Feskens, E.;McCarthy, M.;Riboli, E.;Wareham, N. J.
通讯作者：
Wareham, N. J.
影响因子：
39.3
作者：
Mor, Adi;Luboshits, Galia;George, Jacob
通讯作者：
George, Jacob
DOI：
10.1161/atvbaha.110.206813
发表时间：
2010-09-01
影响因子：
8.7
作者：
Ammirati, Enrico;Cianflone, Domenico;Norata, Giuseppe Danilo
通讯作者：
Norata, Giuseppe Danilo
急性冠脉综合征患者Th17/Treg失衡
影响因子：
8.6
作者：
Cheng, Xiang;Yu, Xian;Liao, Yu-hua
通讯作者：
Liao, Yu-hua