Blood levels of T-Cell Receptor Excision Circles (TRECs) provide an index of exposure to traumatic stress in mice and humans.
Blood levels of T-Cell Receptor Excision Circles (TRECs) provide an index of exposure to traumatic stress in mice and humans.
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DOI：
10.1038/s41398-022-02159-7
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发表时间：
2022-10-03
影响因子：
6.8
通讯作者：
Carlezon, William A.
中科院分区：
文献类型：
--
作者：
McCullough, Kenneth M.;Katrinli, Seyma;Hartmann, Jakob;Lori, Adriana;Klengel, Claudia;Missig, Galen;Klengel, Torsten;Langford, Nicole A.;Newman, Emily L.;Anderson, Kasey J.;Smith, Alicia K.;Carroll, F. Ivy;Ressler, Kerry J.;Carlezon, William A.
暴露在压力下会引发全身的生物变化。越来越多的证据表明，免疫系统功能的改变与压力相关疾病的发展有关，如重度抑郁症和创伤后应激障碍，这增加了人们对识别免疫标记物的兴趣，这些标记物可提供对心理健康的洞察。胸腺中T细胞受体重排和T细胞成熟过程中的切除事件产生称为T细胞受体切除环（TRECs）的环状DNA片段，其可用作胸腺功能和新迁移的T细胞数量的指标。鉴于数据表明，压力会影响胸腺功能，我们研究了TRECs的血液水平是否可以作为一个定量的外周指数的累积压力暴露及其生理相关性。我们假设，慢性应激暴露会损害胸腺功能，并产生相应的TRECs水平下降。在雄性小鼠中，暴露于慢性社会失败压力（CSDS）导致胸腺退化，肾上腺肥大和血液中TRECs水平降低。将这些研究扩展到人类揭示了循环TRECs水平与儿童情感和身体虐待之间的强烈负相关性。细胞类型特异性分析还揭示了TREC水平与血细胞组成之间的关联，以及CD4T +和CD8T +细胞中细胞类型特异性甲基化变化。此外，TREC水平与表观遗传年龄加速相关，表观遗传年龄加速是压力暴露的常见生物标志物。我们的研究结果表明，小鼠和人类的研究结果之间的一致性，并表明，血液传播的TRECs是一种预防性相关的生物标志物，与哺乳动物应激暴露的累积生理和免疫相关影响相关，并提供了深入了解。
Exposure to stress triggers biological changes throughout the body. Accumulating evidence indicates that alterations in immune system function are associated with the development of stress-associated illnesses such as major depressive disorder and post-traumatic stress disorder, increasing interest in identifying immune markers that provide insight into mental health. Recombination events during T-cell receptor rearrangement and T-cell maturation in the thymus produce circular DNA fragments called T-cell receptor excision circles (TRECs) that can be utilized as indicators of thymic function and numbers of newly emigrating T-cells. Given data suggesting that stress affects thymus function, we examined whether blood levels of TRECs might serve as a quantitative peripheral index of cumulative stress exposure and its physiological correlates. We hypothesized that chronic stress exposure would compromise thymus function and produce corresponding decreases in levels of TRECs. In male mice, exposure to chronic social defeat stress (CSDS) produced thymic involution, adrenal hypertrophy, and decreased levels of TRECs in blood. Extending these studies to humans revealed robust inverse correlations between levels of circulating TRECs and childhood emotional and physical abuse. Cell-type specific analyses also revealed associations between TREC levels and blood cell composition, as well as cell-type specific methylation changes in CD4T + and CD8T + cells. Additionally, TREC levels correlated with epigenetic age acceleration, a common biomarker of stress exposure. Our findings demonstrate alignment between findings in mice and humans and suggest that blood-borne TRECs are a translationally-relevant biomarker that correlates with, and provides insight into, the cumulative physiological and immune-related impacts of stress exposure in mammals.
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影响因子：
3.7
作者：
Fichna M;Żurawek M;Słomiński B;Sumińska M;Czarnywojtek A;Rozwadowska N;Fichna P;Myśliwiec M;Ruchała M
通讯作者：
Ruchała M
DOI：
10.4049/jimmunol.2100172
发表时间：
2021-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Finney J;Kelsoe G
通讯作者：
Kelsoe G
影响因子：
120.7
作者：
Binder, Elisabeth B.;Bradley, Rebekah G.;Ressler, Kerry J.
通讯作者：
Ressler, Kerry J.
影响因子：
4.3
作者：
Dedic, Nina;Kuhne, Claudia;Deussing, Jan M.
通讯作者：
Deussing, Jan M.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y