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

• Published in: Nature communications 2019-01, Vol.10 (1), p.229-229, Article 229
• Main Authors: Hsu, Martin, Rayasam, Aditya, Kijak, Julie A., Choi, Yun Hwa, Harding, Jeffrey S., Marcus, Sarah A., Karpus, William J., Sandor, Matyas, Fabry, Zsuzsanna
• Format: Article
• Language: English
• Subjects: 13/51; 14/1; 14/19; 14/34; 59/57; 631/250/1617/290; 631/378/371; 64/60; 82/80; 96/31; Adjuvants, Immunologic - administration & dosage; Animals; Antigens; Antigens - immunology; Antigens - metabolism; Bacteria; Brain - diagnostic imaging; Brain - immunology; Cell Proliferation; Cerebrospinal Fluid - immunology; Circuit design; Circuits; Design engineering; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - diagnostic imaging; Encephalomyelitis, Autoimmune, Experimental - immunology; Ethmoid Bone; Evans Blue - administration & dosage; Female; Heterogeneity; Humanities and Social Sciences; Humans; Immunologic Surveillance - immunology; Lymph nodes; Lymphangiogenesis - immunology; Lymphatic Vessels - diagnostic imaging; Lymphatic Vessels - immunology; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Myelin-Oligodendrocyte Glycoprotein - administration & dosage; Myelin-Oligodendrocyte Glycoprotein - immunology; Operators; Pertussis Toxin - administration & dosage; Pertussis Toxin - immunology; Promoters; Science; Science (multidisciplinary); T-Lymphocytes - immunology; Transcription; Vascular Endothelial Growth Factor C - immunology; Vascular Endothelial Growth Factor C - metabolism; Vascular Endothelial Growth Factor Receptor-3 - immunology; Vascular Endothelial Growth Factor Receptor-3 - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-08163-0

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. Lymphangiogenesis occurs in the context of systemic inflammation and development but has not been reported for the lymphatics that surround the CNS. Here the authors show that in the context of experimental autoimmune encephatlitis, lymphangiogenesis occurs at the cribriform plate, but not the meninges, and contributes to immune cell and antigen drainage.