Cuprizone‐induced demyelination triggers a CD8 ‐pronounced T cell recruitment
| العنوان: | Cuprizone‐induced demyelination triggers a |
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| المؤلفون: | Paul van der Valk, Jiangshan Zhan, Stefan Gingele, Emily Santrau, Sandra Amor, Julia Frenz, Christoph Schmitz, Hannes Kaddatz, Markus Kipp, Julia Nedelcu, Michael Müller, Viktoria Gudi, Martin Stangel, Uta Chrzanowski, Sarah Joost, Brigitte Müller-Hilke, Theresa Greiner |
| المساهمون: | AII - Inflammatory diseases, Amsterdam Neuroscience - Neuroinfection & -inflammation, Pathology |
| المصدر: | GLIA, 69(4), 925-942. John Wiley and Sons Inc. Kaddatz, H, Joost, S, Nedelcu, J, Chrzanowski, U, Schmitz, C, Gingele, S, Gudi, V, Stangel, M, Zhan, J, Santrau, E, Greiner, T, Frenz, J, Müller-Hilke, B, Müller, M, Amor, S, van der Valk, P & Kipp, M 2021, ' Cuprizone-induced demyelination triggers a CD8-pronounced T cell recruitment ', GLIA, vol. 69, no. 4, pp. 925-942 . https://doi.org/10.1002/glia.23937 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, T cell, CD8-Positive T-Lymphocytes, Biology, Cuprizone, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Immune system, Antigen, medicine, Animals, Cytotoxic T cell, Neuroinflammation, Multiple sclerosis, medicine.disease, Oligodendrocyte, Mice, Inbred C57BL, Disease Models, Animal, Oligodendroglia, 030104 developmental biology, medicine.anatomical_structure, Neurology, Immunology, 030217 neurology & neurosurgery, CD8, Demyelinating Diseases |
| الوصف: | The loss of myelinating oligodendrocytes is a key characteristic of many neurological diseases, including Multiple Sclerosis (MS). In progressive MS, where effective treatment options are limited, peripheral immune cells can be found at the site of demyelination and are suggested to play a functional role during disease progression. In this study, we hypothesize that metabolic oligodendrocyte injury, caused by feeding the copper chelator cuprizone, is a potent trigger for peripheral immune cell recruitment into the central nervous system (CNS). We used immunohistochemistry and flow cytometry to evaluate the composition, density, and activation status of infiltrating T lymphocytes in cuprizone-intoxicated mice and post-mortem progressive MS tissues. Our results demonstrate a predominance of CD8+ T cells along with high proliferation rates and cytotoxic granule expression, indicating an antigenic and pro-inflammatory milieu in the CNS of cuprizone-intoxicated mice. Numbers of recruited T cells and the composition of lymphocytic infiltrates in cuprizone-intoxicated mice were found to be comparable to those found in progressive MS lesions. Finally, amelioration of the cuprizone-induced pathology by treating mice with laquinimod significantly reduces the number of recruited T cells. Overall, this study provides strong evidence that toxic demyelination is a sufficient trigger for T cells to infiltrate the demyelinated CNS. Further investigation of the mode of action and functional consequence of T cell recruitment might offer promising new therapeutic approaches for progressive MS. |
| تدمد: | 1098-1136 0894-1491 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cfbb8ce8f3cfd0f6fcf3bd7a2eac8c0e https://doi.org/10.1002/glia.23937 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....cfbb8ce8f3cfd0f6fcf3bd7a2eac8c0e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10981136 08941491 |
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