Mucosal-Associated Invariant T Cells Are Involved in Acute Ischemic Stroke by Regulating Neuroinflammation.
Mucosal-Associated Invariant T Cells Are Involved in Acute Ischemic Stroke by Regulating Neuroinflammation.
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DOI：
10.1161/jaha.120.018803
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发表时间：
2021-04-06
影响因子：
5.4
通讯作者：
Hattori N
中科院分区：
文献类型：
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作者：
Nakajima S;Tanaka R;Yamashiro K;Chiba A;Noto D;Inaba T;Kurita N;Miyamoto N;Kuroki T;Shimura H;Ueno Y;Urabe T;Miyake S;Hattori N
粘液相关的不变T（MAIT）细胞与几种自身免疫性疾病中的炎症有关。然而，它们与缺血性卒中的关系仍不清楚。本研究试图阐明MAIT细胞在小鼠急性缺血性中风中的作用。我们使用MR 1敲除C57 BL/6（MR 1 −/−）小鼠和野生型同窝仔（MR 1 +/+）。在进行短暂的大脑中动脉闭塞（tMCAO）后，我们评估了急性脑缺血与炎症和预后的关系。此外，我们分析了给予抑制性MR 1配体和载体对照的tMCAO C57 BL/6小鼠。我们还通过流式细胞术评估了MAIT细胞向缺血脑中的浸润。结果显示，MR 1 −/−小鼠（n=8）的梗死体积减少，神经功能缺损改善。在MR 1 −/−小鼠的脑梗死区域中，浸润性小胶质细胞/巨噬细胞（n=3-5）的数量及其活化（n=5）减少。在MR 1 −/−小鼠中，tMCAO后24小时（n=3-5）的白细胞介素-6和白细胞介素-17以及tMCAO后72小时（n=5）的白细胞介素-17细胞因子水平较低。抑制性MR 1配体的给药减少了梗死体积并改善了功能障碍（n=5）。流式细胞术分析表明，在tMCAO后24小时，浸润到缺血脑中的MAIT细胞减少（n=17）。我们的研究结果表明，MAIT细胞在局灶性脑缺血后的神经炎症中起着重要作用，并且MAIT细胞调节的使用具有作为治疗急性缺血性卒中的新型神经保护剂的潜在作用。
Mucosal‐associated invariant T (MAIT) cells have been associated with inflammation in several autoimmune diseases. However, their relation to ischemic stroke remains unclear. This study attempted to elucidate the role of MAIT cells in acute ischemic stroke in mice. We used MR1 knockout C57BL/6 (MR1−/−) mice and wild‐type littermates (MR1+/+). After performing a transient middle cerebral artery occlusion (tMCAO), we evaluated the association with inflammation and prognosis in the acute cerebral ischemia. Furthermore, we analyzed the tMCAO C57BL/6 mice administered with the suppressive MR1 ligand and the vehicle control. We also evaluated the infiltration of MAIT cells into the ischemic brain by flow cytometry. Results showed a reduction of infarct volume and an improvement of neurological impairment in MR1−/− mice (n=8). There was a reduction in the number of infiltrating microglia/macrophages (n=3–5) and in their activation (n=5) in the peri‐infarct area of MR1−/− mice. The cytokine levels of interleukin‐6 and interleukin‐17 at 24 hours after tMCAO (n=3–5), and for interleukin‐17 at 72 hours after tMCAO (n=5), were lower in the MR1−/− mice. The administration of the suppressive MR1 ligand reduced the infarct volume and improved functional impairment (n=5). Flow cytometric analysis demonstrated there was a reduction of MAIT cells infiltrating into the ischemic brain at 24 hours after tMCAO (n=17). Our results showed that MAIT cells play an important role in neuroinflammation after focal cerebral ischemia and the use of MAIT cell regulation has a potential role as a novel neuroprotectant for the treatment of acute ischemic stroke.