The choroid plexus is a key cerebral invasion route for T cells after stroke
The choroid plexus is a key cerebral invasion route for T cells after stroke
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DOI：
10.1007/s00401-017-1758-y
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发表时间：
2017-12-01
影响因子：
12.7
通讯作者：
Liesz, Arthur
中科院分区：
文献类型：
--
作者：
Llovera, Gemma;Benakis, Corinne;Liesz, Arthur
神经炎症对中风病理生理学有很大影响。外周白细胞（尤其是 T 细胞）的脑侵袭已被证明是促进中风后炎症组织损伤的关键事件。虽然之前的研究主要集中在 T 细胞血管侵入缺血性脑部，但脉络丛 (ChP) 作为中风后脑部 T 细胞侵入的替代途径尚未得到研究。我们在这里报告了梗死周围皮层中 T 细胞的特异性积累，并检测到 T 细胞作为小鼠同侧 ChP 以及人类中风后尸检样本中的主要群体。通过光激活 T 细胞的体内细胞追踪证实了 T 细胞从 ChP 迁移到梗塞周围皮层。反过来，在同侧 ChP 发生光血栓损伤后以及在包含 ChP 缺血的中风模型中，侵入缺血脑的 T 细胞显着减少。我们检测到 CCR2 配体的梯度作为潜在的驱动力，并描述了脑内迁移的神经解剖学途径。总之，我们的研究表明 ChP 是中风后脑 T 细胞侵袭的关键侵袭途径，并将皮质和 ChP 之间的 CCR2 配体梯度描述为该侵袭途径的潜在驱动机制。
Neuroinflammation contributes substantially to stroke pathophysiology. Cerebral invasion of peripheral leukocytes-particularly T cells-has been shown to be a key event promoting inflammatory tissue damage after stroke. While previous research has focused on the vascular invasion of T cells into the ischemic brain, the choroid plexus (ChP) as an alternative cerebral T-cell invasion route after stroke has not been investigated. We here report specific accumulation of T cells in the peri-infarct cortex and detection of T cells as the predominant population in the ipsilateral ChP in mice as well as in human post-stroke autopsy samples. T-cell migration from the ChP to the peri-infarct cortex was confirmed by in vivo cell tracking of photoactivated T cells. In turn, significantly less T cells invaded the ischemic brain after photothrombotic lesion of the ipsilateral ChP and in a stroke model encompassing ChP ischemia. We detected a gradient of CCR2 ligands as the potential driving force and characterized the neuroanatomical pathway for the intracerebral migration. In summary, our study demonstrates that the ChP is a key invasion route for post-stroke cerebral T-cell invasion and describes a CCR2-ligand gradient between cortex and ChP as the potential driving mechanism for this invasion route.