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Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells

There are no conventional lymphatic vessels within the CNS parenchyma, although it has been hypothesized that lymphatics near the cribriform plate or dura maintain fluid homeostasis and immune surveillance during steady-state conditions. However, the role of these lymphatic vessels during neuroinfla...

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Autores principales: Hsu, Martin, Rayasam, Aditya, Kijak, Julie A., Choi, Yun Hwa, Harding, Jeffrey S., Marcus, Sarah A., Karpus, William J., Sandor, Matyas, Fabry, Zsuzsanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335416/
https://www.ncbi.nlm.nih.gov/pubmed/30651548
http://dx.doi.org/10.1038/s41467-018-08163-0
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author Hsu, Martin
Rayasam, Aditya
Kijak, Julie A.
Choi, Yun Hwa
Harding, Jeffrey S.
Marcus, Sarah A.
Karpus, William J.
Sandor, Matyas
Fabry, Zsuzsanna
author_facet Hsu, Martin
Rayasam, Aditya
Kijak, Julie A.
Choi, Yun Hwa
Harding, Jeffrey S.
Marcus, Sarah A.
Karpus, William J.
Sandor, Matyas
Fabry, Zsuzsanna
author_sort Hsu, Martin
collection PubMed
description There are no conventional lymphatic vessels within the CNS parenchyma, although it has been hypothesized that lymphatics near the cribriform plate or dura maintain fluid homeostasis and immune surveillance during steady-state conditions. However, the role of these lymphatic vessels during neuroinflammation is not well understood. We report that lymphatic vessels near the cribriform plate undergo lymphangiogenesis in a VEGFC – VEGFR3 dependent manner during experimental autoimmune encephalomyelitis (EAE) and drain both CSF and cells that were once in the CNS parenchyma. Lymphangiogenesis also contributes to the drainage of CNS derived antigens that leads to antigen specific T cell proliferation in the draining lymph nodes during EAE. In contrast, meningeal lymphatics do not undergo lymphangiogenesis during EAE, suggesting heterogeneity in CNS lymphatics. We conclude that increased lymphangiogenesis near the cribriform plate can contribute to the management of neuroinflammation-induced fluid accumulation and immune surveillance.
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spelling pubmed-63354162019-01-18 Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells Hsu, Martin Rayasam, Aditya Kijak, Julie A. Choi, Yun Hwa Harding, Jeffrey S. Marcus, Sarah A. Karpus, William J. Sandor, Matyas Fabry, Zsuzsanna Nat Commun Article There are no conventional lymphatic vessels within the CNS parenchyma, although it has been hypothesized that lymphatics near the cribriform plate or dura maintain fluid homeostasis and immune surveillance during steady-state conditions. However, the role of these lymphatic vessels during neuroinflammation is not well understood. We report that lymphatic vessels near the cribriform plate undergo lymphangiogenesis in a VEGFC – VEGFR3 dependent manner during experimental autoimmune encephalomyelitis (EAE) and drain both CSF and cells that were once in the CNS parenchyma. Lymphangiogenesis also contributes to the drainage of CNS derived antigens that leads to antigen specific T cell proliferation in the draining lymph nodes during EAE. In contrast, meningeal lymphatics do not undergo lymphangiogenesis during EAE, suggesting heterogeneity in CNS lymphatics. We conclude that increased lymphangiogenesis near the cribriform plate can contribute to the management of neuroinflammation-induced fluid accumulation and immune surveillance. Nature Publishing Group UK 2019-01-16 /pmc/articles/PMC6335416/ /pubmed/30651548 http://dx.doi.org/10.1038/s41467-018-08163-0 Text en © The Author(s) 2019 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/.
spellingShingle Article
Hsu, Martin
Rayasam, Aditya
Kijak, Julie A.
Choi, Yun Hwa
Harding, Jeffrey S.
Marcus, Sarah A.
Karpus, William J.
Sandor, Matyas
Fabry, Zsuzsanna
Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells
title Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells
title_full Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells
title_fullStr Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells
title_full_unstemmed Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells
title_short Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells
title_sort neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of cns-derived antigens and immune cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335416/
https://www.ncbi.nlm.nih.gov/pubmed/30651548
http://dx.doi.org/10.1038/s41467-018-08163-0
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