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

Author

Listed:
  • Martin Hsu

    (University of Wisconsin-Madison)

  • Aditya Rayasam

    (University of Wisconsin-Madison)

  • Julie A. Kijak

    (University of Wisconsin-Madison)

  • Yun Hwa Choi

    (University of Wisconsin-Madison)

  • Jeffrey S. Harding

    (Mount Sinai Hospital)

  • Sarah A. Marcus

    (University of Wisconsin-Madison)

  • William J. Karpus

    (University of Wisconsin-Madison)

  • Matyas Sandor

    (University of Wisconsin-Madison)

  • Zsuzsanna Fabry

    (University of Wisconsin-Madison)

Abstract

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.

Suggested Citation

  • Martin Hsu & Aditya Rayasam & Julie A. Kijak & Yun Hwa Choi & Jeffrey S. Harding & Sarah A. Marcus & William J. Karpus & Matyas Sandor & Zsuzsanna Fabry, 2019. "Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08163-0
    DOI: 10.1038/s41467-018-08163-0
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    Cited by:

    1. Jingying Chen & Jing Ding & Yongyu Li & Fujuan Feng & Yuhang Xu & Tao Wang & Jianbo He & Jing Cang & Lingfei Luo, 2024. "Epidermal growth factor-like domain 7 drives brain lymphatic endothelial cell development through integrin αvβ3," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Weiping Dai & Mengqian Yang & Pei Xia & Chuan Xiao & Shuying Huang & Zhan Zhang & Xin Cheng & Wenchang Li & Jian Jin & Jingyun Zhang & Binghuo Wu & Yingying Zhang & Pei-hui Wu & Yangyang Lin & Wen Wu , 2022. "A functional role of meningeal lymphatics in sex difference of stress susceptibility in mice," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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