Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Neuroinflammation. 2023 Apr 3;20(1):89. doi: 10.1186/s12974-023-02772-3.
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are activated and play a pivotal role in response to tissue injury. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by microglia and promotes microglial activation, survival and phagocytosis. Here, we identify a critical role for TREM2 in microglial activation and function during AQP4-IgG and complement-induced demyelination. TREM2-deficient mice had more severe tissue damage and neurological impairment, as well as fewer oligodendrocytes with suppressed proliferation and maturation. The number of microglia clustering in NMOSD lesions and their proliferation were reduced in TREM2-deficient mice. Moreover, morphology analysis and expression of classic markers showed compromised activation of microglia in TREM2-deficient mice, which was accompanied by suppressed phagocytosis and degradation of myelin debris by microglia. These results overall indicate that TREM2 is a key regulator of microglial activation and exert neuroprotective effects in NMOSD demyelination.
视神经脊髓炎谱系疾病（NMOSD）是一种由自身免疫机制引发的中枢神经系统（CNS）炎症性脱髓鞘疾病。小胶质细胞被激活，并在应对组织损伤时发挥关键作用。髓系细胞触发受体 2（TREM2）表达于小胶质细胞，并促进小胶质细胞的激活、存活和吞噬作用。在这里，我们确定了 TREM2 在 AQP4-IgG 和补体诱导的脱髓鞘过程中小胶质细胞激活和功能中的关键作用。TREM2 缺陷型小鼠具有更严重的组织损伤和神经功能障碍，少突胶质细胞增殖和成熟受到抑制。TREM2 缺陷型小鼠 NMOSD 病变中的小胶质细胞聚集数量减少，其增殖也减少。此外，形态分析和经典标志物的表达表明 TREM2 缺陷型小鼠中小胶质细胞的激活受到损害，这伴随着吞噬作用和小胶质细胞对髓鞘碎片的降解受到抑制。这些结果总体表明，TREM2 是小胶质细胞激活的关键调节因子，并在 NMOSD 脱髓鞘中发挥神经保护作用。
Zotero 插件
