Cortisol-induced immune suppression by a blockade of lymphocyte egress in traumatic brain injury.
Cortisol-induced immune suppression by a blockade of lymphocyte egress in traumatic brain injury.
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DOI：
10.1186/s12974-016-0663-y
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发表时间：
2016-08-25
影响因子：
9.3
通讯作者：
Wu MX
中科院分区：
文献类型：
--
作者：
Dong T;Zhi L;Bhayana B;Wu MX
急性创伤性脑损伤（TBI）是美国死亡和残疾的主要原因之一。神经炎症被认为是有益的和有害的，可能在一个时间依赖性的方式。为了解决神经炎症在脑损伤中的作用，通过标准控制的皮质撞击使C57 BL/6小鼠经受闭合头部轻度TBI（mTBI），沿着有或没有1-磷酸鞘氨醇（S1 P）或咯利普兰的处理，之后通过组织学评价撞击部位的脑组织的细胞形态，通过qRT-PCR和T细胞染色评价炎症，Caspase-3和TUNEL染色显示细胞死亡。通过流式细胞术定量循环淋巴细胞，并通过LC-MS/MS分析血浆氢化可的松。为了研究皮质醇降低外周T细胞数量的机制，氢化可的松给药后，通过活体共聚焦显微镜在淋巴结中追踪T细胞出口。我们检测到循环淋巴细胞的数量减少，特别是，T细胞后不久mTBI，这是呈负相关的血浆皮质醇的短暂和强劲的增加。皮质醇抑制T细胞从次级淋巴组织逸出的能力证明，短暂性淋巴细胞减少症可能部分由皮质醇通过阻断淋巴细胞逸出引起。此外，外源性氢化可的松严重抑制未受伤小鼠的外周淋巴细胞，而给予出口促进剂S1 P使mTBI小鼠的循环T细胞正常化，并增加受伤大脑中的T细胞。同样，rolipram，一种cAMP磷酸二酯酶抑制剂，也能够在体外氢化可的松的存在下提高T细胞中的cAMP水平，并消除皮质醇在mTBI小鼠中的作用。研究表明，在TBI的早期阶段的循环T细胞的数量与T细胞浸润和炎症反应，以及在大脑皮层和海马的细胞死亡的影响网站下方呈正相关。细胞内cAMP的减少可能是皮质醇介导的T细胞出口阻滞机制的一部分。该研究有力地论证了皮质醇诱导的免疫抑制在TBI早期的保护作用。
Acute traumatic brain injury (TBI) represents one of major causes of mortality and disability in the USA. Neuroinflammation has been regarded both beneficial and detrimental, probably in a time-dependent fashion. To address a role for neuroinflammation in brain injury, C57BL/6 mice were subjected to a closed head mild TBI (mTBI) by a standard controlled cortical impact, along with or without treatment of sphingosine 1-phosphate (S1P) or rolipram, after which the brain tissue of the impact site was evaluated for cell morphology via histology, inflammation by qRT-PCR and T cell staining, and cell death with Caspase-3 and TUNEL staining. Circulating lymphocytes were quantified by flow cytometry, and plasma hydrocortisone was analyzed by LC-MS/MS. To investigate the mechanism whereby cortisol lowered the number of peripheral T cells, T cell egress was tracked in lymph nodes by intravital confocal microscopy after hydrocortisone administration. We detected a decreased number of circulating lymphocytes, in particular, T cells soon after mTBI, which was inversely correlated with a transient and robust increase of plasma cortisol. The transient lymphocytopenia might be caused by cortisol in part via a blockade of lymphocyte egress as demonstrated by the ability of cortisol to inhibit T cell egress from the secondary lymphoid tissues. Moreover, exogenous hydrocortisone severely suppressed periphery lymphocytes in uninjured mice, whereas administering an egress-promoting agent S1P normalized circulating T cells in mTBI mice and increased T cells in the injured brain. Likewise, rolipram, a cAMP phosphodiesterase inhibitor, was also able to elevate cAMP levels in T cells in the presence of hydrocortisone in vitro and abrogate the action of cortisol in mTBI mice. The investigation demonstrated that the number of circulating T cells in the early phase of TBI was positively correlated with T cell infiltration and inflammatory responses as well as cell death at the cerebral cortex and hippocampus beneath the impact site. Decreases in intracellular cAMP might be part of the mechanism behind cortisol-mediated blockade of T cell egress. The study argues strongly for a protective role of cortisol-induced immune suppression in the early stage of TBI.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
4.1
作者：
Coutinho, Agnes E.;Chapman, Karen E.
通讯作者：
Chapman, Karen E.
影响因子：
6.3
作者：
Dong, Tingting;Zhang, Qi;Wu, Mei X.
通讯作者：
Wu, Mei X.
DOI：
10.1038/icb.1979.49
发表时间：
1979-01-01
期刊：
AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE
影响因子：
--
作者：
BOLTON, PM;KIROV, SM;DONALD, KJ
通讯作者：
DONALD, KJ
影响因子：
4.3
作者：
COX, JH;FORD, WL
通讯作者：
FORD, WL