Triggering receptor expressed on myeloid cells-2 expression in the brain is required for maximal phagocytic activity and improved neurological outcomes following experimental stroke
Triggering receptor expressed on myeloid cells-2 expression in the brain is required for maximal phagocytic activity and improved neurological outcomes following experimental stroke
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DOI：
10.1177/0271678x18817282
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发表时间：
2019-10-01
影响因子：
6.3
通讯作者：
Yenari, Midori A.
中科院分区：
文献类型：
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作者：
Kurisu, Kota;Zheng, Zhen;Yenari, Midori A.
髓样细胞上表达的触发受体-2 （TREM2）是一种先天免疫受体，可促进髓样细胞如小胶质细胞和巨噬细胞的吞噬。我们之前的研究表明，TREM2缺乏恶化了实验性脑卒中的预后，并阻碍了吞噬。然而，参与卒中病理的髓系细胞包括脑常驻小胶质细胞和循环巨噬细胞。我们现在通过生成骨髓嵌合小鼠来阐明脑小胶质细胞或循环巨噬细胞上的TREM2是否有助于其在缺血性卒中中的有益作用。用tre2敲除小鼠（KO）或野生型小鼠（Wt）的BM嵌合体小鼠作为供体小鼠和受体小鼠。小鼠遭受实验性脑卒中，评估神经功能和梗死体积。与缺乏TREM2的小鼠相比，脑小胶质细胞中TREM2完整的小鼠表现出更好的神经恢复和减少的梗死体积。与脑TREM2完整的小鼠相比，缺乏脑TREM2的小鼠骨髓细胞活化和吞噬细胞数量减少。这些结果表明，TREM2的表达对卒中后恢复很重要，并且TREM2在脑驻留小胶质细胞上的表达比在循环巨噬细胞上的表达对卒中后恢复更重要。这些发现可能为脑血管疾病的治疗提供新的靶点。
Triggering receptor expressed on myeloid cells-2 (TREM2) is an innate immune receptor that promotes phagocytosis by myeloid cells such as microglia and macrophages. We previously showed that TREM2 deficiency worsened outcomes from experimental stroke and impeded phagocytosis. However, myeloid cells participating in stroke pathology include both brain resident microglia and circulating macrophages. We now clarify whether TREM2 on brain microglia or circulating macrophages contribute to its beneficial role in ischemic stroke by generating bone marrow (BM) chimeric mice. BM chimera mice from TREM2 knockout (KO) or wild type (Wt) mice were used as donor and recipient mice. Mice were subjected to experimental stroke, and neurological function and infarct volume were assessed. Mice with intact TREM2 in brain microglia showed better neurological recovery and reduced infarct volumes, compared with mice lacking microglial TREM2. Myeloid cell activation and numbers of phagocytes were decreased in mice lacking brain TREM2, compared with mice with intact brain TREM2. These results suggest that TREM2 expression is important for post-stroke recovery, and that TREM2 expression on brain resident microglia is more essential to this recovery, than that of circulating macrophages. These findings might suggest a new therapeutic target for cerebrovascular diseases.