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Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage

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Title
Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage
Author(s)
Jin-Hui Yoon; Hokyung Jin; Kim, Hae Jin; Seon Pyo Hong; Myung Jin Yang; Ji Hoon Ahn; Young-Chan Kim; Seo, Jincheol; Lee, Yongjeon; McDonald, Donald M.; Davis, Michael J.; Gou Young Koh
Publication Date
2024-01
Journal
Nature, v.625, no.7996, pp.768 - 777
Publisher
Nature Publishing Group
Abstract
Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes 1–17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice 18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial. © 2024, The Author(s).
URI
https://pr.ibs.re.kr/handle/8788114/15019
DOI
10.1038/s41586-023-06899-4
ISSN
0028-0836
Appears in Collections:
Center for Vascular Research(혈관 연구단) > 1. Journal Papers (저널논문)
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