Journal article
Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination
- Abstract:
- The precise neurophysiological changes prompted by meningeal lymphatic dysfunction remain unclear. Here, we showed that inducing meningeal lymphatic vessel ablation in adult mice led to gene expression changes in glial cells, followed by reductions in mature oligodendrocyte numbers and specific lipid species in the brain. These phenomena were accompanied by altered meningeal adaptive immunity and brain myeloid cell activation. During brain remyelination, meningeal lymphatic dysfunction provoked a state of immunosuppression that contributed to delayed spontaneous oligodendrocyte replenishment and axonal loss. The deficiencies in mature oligodendrocytes and neuroinflammation due to impaired meningeal lymphatic function were solely recapitulated in immunocompetent mice. Patients diagnosed with multiple sclerosis presented reduced vascular endothelial growth factor C in the cerebrospinal fluid, particularly shortly after clinical relapses, possibly indicative of poor meningeal lymphatic function. These data demonstrate that meningeal lymphatics regulate oligodendrocyte function and brain myelination, which might have implications for human demyelinating diseases.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
-
-
(Preview, Accepted manuscript, pdf, 291.3KB, Terms of use)
-
- Publisher copy:
- 10.1016/j.immuni.2024.08.004
Authors
+ Wellcome Trust
More from this funder
- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 104079/Z/14/Z
+ Medical Research Council
More from this funder
- Funder identifier:
- https://ror.org/03x94j517
- Grant:
- MR/V007173/1
- Publisher:
- Cell Press
- Journal:
- Immunity More from this journal
- Volume:
- 57
- Issue:
- 10
- Pages:
- 2328-2343.e8
- Publication date:
- 2024-08-31
- Acceptance date:
- 2024-08-02
- DOI:
- EISSN:
-
1097-4180
- ISSN:
-
1074-7613
- Pmid:
-
39217987
- Language:
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English
- Keywords:
- Pubs id:
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2027120
- Local pid:
-
pubs:2027120
- Deposit date:
-
2025-02-05
Terms of use
- Copyright holder:
- Elsevier Inc.
- Copyright date:
- 2024
- Rights statement:
- © 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
- Notes:
-
This research was funded in part by a senior clinical fellowship from the Medical Research Council [MR/V007173/1], Wellcome Trust Fellowship [104079/Z/14/Z] and by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), to S.R.I., and a Guarantors of Brain Fellowship to M.M.. For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript (AAM) version arising from this submission.
This is the accepted manuscript version of the article. The final version is available online from Elsevier at https://dx.doi.org/10.1016/j.immuni.2024.08.004
- Licence:
- CC Attribution (CC BY)
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