γδ T Cells Contribute to Injury in the Developing Brain.
γδ T Cells Contribute to Injury in the Developing Brain.
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γ δ T 细胞会导致发育中的大脑损伤
DOI：
10.1016/j.ajpath.2017.11.012
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Albertsson AM;Zhang X;Vontell R;Bi D;Bronson RT;Supramaniam V;Baburamani AA;Hua S;Nazmi A;Cardell S;Zhu C;Cantor H;Mallard C;Hagberg H;Leavenworth JW;Wang X
早产儿脑损伤，特别是脑室周围白质软化，是导致神经功能障碍的重要原因。炎症有助于围产期脑损伤的发展，但导致早期脑损伤的重要介质仍然在很大程度上未知。新生儿的常规αβ T细胞反应能力降低。然而，γδT细胞在早期发育过程中已经具有功能能力，并且在早期生命免疫中很重要。我们研究了γδT细胞对早产儿脑损伤的潜在作用，使用了患有脑室周围白质软化症的早产儿的死后脑和两种早产儿脑损伤的动物模型-缺氧缺血小鼠模型和胎羊窒息模型。损伤后，在小鼠、绵羊和死后早产儿的大脑中观察到大量的γδT细胞，γδT细胞的耗尽为小鼠模型提供了保护。常见的γδ T细胞相关细胞因子干扰素-γ和IL-17 A在脑中未检测到。虽然有IL-17 f和IL-22的mRNA水平增加，在小鼠脑损伤后，无论是IL-17 F还是IL-22细胞因子有助于早产儿脑损伤。这些发现突出了发育中大脑损伤的独特特征，与成熟大脑中的损伤不同，γδT细胞独立于常见的γδ T细胞相关细胞因子而作为损伤的引发剂发挥作用。这一发现将有助于确定预防或治疗早产儿脑损伤的治疗靶点。
Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurologic disabilities. Inflammation contributes to perinatal brain injury development, but the essential mediators that lead to early-life brain injury remain largely unknown. Neonates have reduced capacity for mounting conventional αβT-cell responses. However, γδT cells are already functionally competent during early development and are important in early-life immunity. We investigated the potential contribution of γδT cells to preterm brain injury using postmortem brains from human preterm infants with periventricular leukomalacia and two animal models of preterm brain injury—the hypoxic-ischemic mouse model and a fetal sheep asphyxia model. Large numbers of γδT cells were observed in the brains of mice, sheep, and postmortem preterm infants after injury, and depletion of γδT cells provided protection in the mouse model. The common γδT-cell–associated cytokines interferon-γ and IL-17A were not detectable in the brain. Although there were increased mRNA levels of Il17f and Il22 in the mouse brains after injury, neither IL-17F nor IL-22 cytokines contributed to preterm brain injury. These findings highlight unique features of injury in the developing brain, where, unlike injury in the mature brain, γδT cells function as initiators of injury independently of common γδT-cell–associated cytokines. This finding will help to identify therapeutic targets for preventing or treating preterm infants with brain injury.
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影响因子：
9.3
作者：
Albertsson AM;Bi D;Duan L;Zhang X;Leavenworth JW;Qiao L;Zhu C;Cardell S;Cantor H;Hagberg H;Mallard C;Wang X
通讯作者：
Wang X
DOI：
10.4049/jimmunol.0903679
发表时间：
2010-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Born WK;Yin Z;Hahn YS;Sun D;O'Brien RL
通讯作者：
O'Brien RL
影响因子：
82.9
作者：
Liesz, Arthur;Suri-Payer, Elisabeth;Veltkamp, Roland
通讯作者：
Veltkamp, Roland
影响因子：
20.3
作者：
Gelderblom, Mathias;Weymar, Anna;Magnus, Tim
通讯作者：
Magnus, Tim
影响因子：
5.3
作者：
Craig, A;Luo, NL;Back, SA
通讯作者：
Back, SA