TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder
Abstract 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 (TR...
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-023-02772-3 |
| _version_ | 1827970365268164608 |
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| author | Yun-Fan You Man Chen Yue Tang Wen-Xiang Yu Xiao-Wei Pang Yun-Hui Chu Hang Zhang Ke Shang Gang Deng Luo-Qi Zhou Sheng Yang Wei Wang Jun Xiao Dai-Shi Tian Chuan Qin |
| author_facet | Yun-Fan You Man Chen Yue Tang Wen-Xiang Yu Xiao-Wei Pang Yun-Hui Chu Hang Zhang Ke Shang Gang Deng Luo-Qi Zhou Sheng Yang Wei Wang Jun Xiao Dai-Shi Tian Chuan Qin |
| author_sort | Yun-Fan You |
| collection | DOAJ |
| description | Abstract 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. Graphical Abstract |
| first_indexed | 2024-04-09T18:52:44Z |
| format | Article |
| id | doaj.art-640bed233aa54a44b7d224c0af3bb0b4 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-09T18:52:44Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-640bed233aa54a44b7d224c0af3bb0b42023-04-09T11:22:58ZengBMCJournal of Neuroinflammation1742-20942023-04-0120111410.1186/s12974-023-02772-3TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorderYun-Fan You0Man Chen1Yue Tang2Wen-Xiang Yu3Xiao-Wei Pang4Yun-Hui Chu5Hang Zhang6Ke Shang7Gang Deng8Luo-Qi Zhou9Sheng Yang10Wei Wang11Jun Xiao12Dai-Shi Tian13Chuan Qin14Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s12974-023-02772-3TREM2MicrogliaNeuromyelitis optica spectrum disorderDemyelination |
| spellingShingle | Yun-Fan You Man Chen Yue Tang Wen-Xiang Yu Xiao-Wei Pang Yun-Hui Chu Hang Zhang Ke Shang Gang Deng Luo-Qi Zhou Sheng Yang Wei Wang Jun Xiao Dai-Shi Tian Chuan Qin TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder Journal of Neuroinflammation TREM2 Microglia Neuromyelitis optica spectrum disorder Demyelination |
| title | TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder |
| title_full | TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder |
| title_fullStr | TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder |
| title_full_unstemmed | TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder |
| title_short | TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder |
| title_sort | trem2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder |
| topic | TREM2 Microglia Neuromyelitis optica spectrum disorder Demyelination |
| url | https://doi.org/10.1186/s12974-023-02772-3 |
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