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TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder
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 e...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069075/ https://www.ncbi.nlm.nih.gov/pubmed/37013543 http://dx.doi.org/10.1186/s12974-023-02772-3 |
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author | You, Yun-Fan Chen, Man Tang, Yue Yu, Wen-Xiang Pang, Xiao-Wei Chu, Yun-Hui Zhang, Hang Shang, Ke Deng, Gang Zhou, Luo-Qi Yang, Sheng Wang, Wei Xiao, Jun Tian, Dai-Shi Qin, Chuan |
author_facet | You, Yun-Fan Chen, Man Tang, Yue Yu, Wen-Xiang Pang, Xiao-Wei Chu, Yun-Hui Zhang, Hang Shang, Ke Deng, Gang Zhou, Luo-Qi Yang, Sheng Wang, Wei Xiao, Jun Tian, Dai-Shi Qin, Chuan |
author_sort | You, Yun-Fan |
collection | PubMed |
description | 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02772-3. |
format | Online Article Text |
id | pubmed-10069075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100690752023-04-04 TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder You, Yun-Fan Chen, Man Tang, Yue Yu, Wen-Xiang Pang, Xiao-Wei Chu, Yun-Hui Zhang, Hang Shang, Ke Deng, Gang Zhou, Luo-Qi Yang, Sheng Wang, Wei Xiao, Jun Tian, Dai-Shi Qin, Chuan J Neuroinflammation Research 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-023-02772-3. BioMed Central 2023-04-03 /pmc/articles/PMC10069075/ /pubmed/37013543 http://dx.doi.org/10.1186/s12974-023-02772-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research You, Yun-Fan Chen, Man Tang, Yue Yu, Wen-Xiang Pang, Xiao-Wei Chu, Yun-Hui Zhang, Hang Shang, Ke Deng, Gang Zhou, Luo-Qi Yang, Sheng Wang, Wei Xiao, Jun Tian, Dai-Shi Qin, Chuan TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder |
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 | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069075/ https://www.ncbi.nlm.nih.gov/pubmed/37013543 http://dx.doi.org/10.1186/s12974-023-02772-3 |
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