[Role of T lymphocytes in ischemic brain injury].
[Role of T lymphocytes in ischemic brain injury].
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T淋巴细胞在缺血性脑损伤中的作用
DOI：
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
A. Yoshimura
中科院分区：
文献类型：
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作者：
T. Shichita;F. Konoeda;A. Yoshimura
近年来，炎症被认为与脑缺血损伤的进展有关。尤其是T淋巴细胞在发病24小时后即可进入脑内，但这些T淋巴细胞的功能和亚群还不完全清楚。通过使用细胞因子缺陷小鼠的短暂性局灶性脑缺血模型，我们发现IL-23和IL-17而不是IL-6或干扰素-γ在缺血性脑损伤中起关键作用。我们发现，主要由浸润性巨噬细胞产生的IL-23可诱导缺血脑内产生IL-17的T淋巴细胞。IL-23和IL-17的表达分别在缺血后1d和3d升高，并通过增加神经毒性因子的表达而促进炎症反应。令我们惊讶的是，IL-17主要由γδT淋巴细胞产生，而不是辅助T细胞。基于这些发现，我们试图为脑梗塞的进展开发新的治疗策略。我们发现给予FTY720(Fingolimod)和抗γδT淋巴细胞抗体可减轻缺血性脑损伤。此外，同时中和IL-23和IL-12的p40抗体也有效。因此，抗细胞因子治疗将适用于脑缺血延迟期的神经保护。
Recently, inflammation has been implicated in the progression of cerebral ischemic injury. Especially, T lymphocytes have been shown to infiltrate into the ischemic brain 24 hours after the onset, however, the function and specific subpopulation of these infiltrated T lymphocytes have not been fully understood. By using cytokine-deficient mice with transient focal ischemia model, we have shown that IL-23 and IL-17 but not IL-6 or IFN-γ play pivotal roles in the ischemic brain injury. We found that IL-23, which was mainly produced from infiltrated macrophages, induced IL-17-producing T lymphocytes in the ischemic brain. IL-23 and IL-17 expression increased 1 day or 3 day after ischemic injury, respectively, and promoted inflammatory responses by increasing the expression of neurotoxic factors. To our surprise, IL-17 was mainly produced by γδT lymphocytes, but not helper T cells. Based on these findings, we have tried to develop new therapeutic strategy for the progression of brain infarction. We found that administration of FTY720 (Fingolimod) and antibody against γδT lymphocytes attenuated ischemic brain damage. Furthermore, antibody against p40 which neutralizes both IL-23 and IL-12 simultaneously was also effective. Therefore, anti-cytokine therapy will be applicable for neuroprotection in the delayed phase of brain ischemia.
影响因子：
32.4
作者：
Kang Z;Altuntas CZ;Gulen MF;Liu C;Giltiay N;Qin H;Liu L;Qian W;Ransohoff RM;Bergmann C;Stohlman S;Tuohy VK;Li X
通讯作者：
Li X