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Neurons promote encephalitogenic CD4+ lymphocyte infiltration in experimental autoimmune encephalomyelitis
http://hdl.handle.net/10458/0002000151
http://hdl.handle.net/10458/00020001510e566dc9-0068-4416-b1ea-04b2e49a2e20
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本文 (4.6 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||||||
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| 公開日 | 2023-10-26 | |||||||||
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| タイトル | Neurons promote encephalitogenic CD4+ lymphocyte infiltration in experimental autoimmune encephalomyelitis | |||||||||
| 言語 | en | |||||||||
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| 言語 | eng | |||||||||
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| 資源タイプ | journal article | |||||||||
| 著者 |
中里, 祐毅
× 中里, 祐毅× Fujita, Yuki
× 中里, 雅光× Yamashita, Toshihide
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| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, leading to demyelination and axonal degeneration. Neuronal excitotoxity mediated by Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) results in neuronal damage in experimental autoimmune encephalitis (EAE), an animal model of MS. Here, we define a critical role of excitatory neurons in the pathogenesis of CD4+ lymphocyte accumulation in EAE. We silenced the activity of excitatory neurons in a mouse model of targeted EAE using inhibitory designer receptors exclusively activated by designer drugs (DREADD) under a CaMKIIα promoter. Neuronal silencing mitigated clinical disease scores in EAE, reduced the expression of c-fos, Tnfα, Ccl2, and Ccr2 mRNAs in targeted EAE lesions, and prevented the migration of CD4+ lymphocytes towards neurons. Ccl2 shRNA treatment of targeted EAE suppressed the migration of CD4+ lymphocytes and alleviated the motor deficits of EAE. Our findings indicate that neuronal activation in EAE promotes the migration of CCR2+ CD4+ lymphocytes and that neuronal silencing with an inhibitory DREADD alleviates clinical and molecular markers of disease. Neuronal CCL2 is thought to be involved in promoting lymphocytes migration. | |||||||||
| 言語 | en | |||||||||
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| 内容記述タイプ | Other | |||||||||
| 内容記述 | Citation: Nakazato, Y., Fujita, Y., Nakazato, M. et al. Neurons promote encephalitogenic CD4+ lymphocyte infiltration in experimental autoimmune encephalomyelitis. Sci Rep 10, 7354 (2020). https://doi.org/10.1038/s41598-020-64363-z |
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| 言語 | en | |||||||||
| 書誌情報 |
en : Scientific Reports 巻 10, 号 1, p. 7354 (2020), 発行日 2020-04-30 |
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| 出版者 | Springer Nature | |||||||||
| 言語 | en | |||||||||
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| 関連タイプ | isVersionOf | |||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | https://doi.org/10.1038/s41598-020-64363-z | |||||||||
| 権利 | ||||||||||
| 言語 | en | |||||||||
| 権利情報 | Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. | |||||||||
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| 出版タイプ | VoR | |||||||||
