Targeting endothelial CD146 attenuates neuroinflammation by limiting lymphocyte extravasation to the CNS
Open accessAbstract
The ability to selectively block the entry of leukocytes into the central nervous system (CNS) without compromising the immune system is an attractive therapeutic approach for treating multiple sclerosis (MS). Using endothelial CD146-deficienct mice as a MS model, we found that endothelial CD146 plays an active role in the CNS-directed extravasation of encephalitogenic T cells, including CD146(+) TH1 and TH17 lymphocytes. Moreover, treating both active and passive MS models with the anti-CD146 antibody AA98 significantly decreased the infiltrated lymphocytes in the CNS and decreased neuroinflammation. Interestingly, the ability of AA98 to inhibit the migration of CD146(+) lymphocytes was dependent on targeting endothelial CD146, but not lymphocytic CD146. These results suggest a key molecular target located on the blood-brain barrier endothelium that mediates the extravasation of inflammatory cells into the CNS. In addition, our data suggest that the AA98 is a promising candidate for treating MS and other CNS autoimmune diseases.
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MCAM can facilitate the accumulation of autoreactive T cells in the CNS during MOG33-55 EAE.
“Another adhesion molecule that can facilitate the accumulation of autoreactive T cells in the CNS during MOG33-55 EAE is melanoma cell adhesion molecule (MCAM) (122, 123).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [122]
Injection of anti-MCAM antibodies into mice reduces the severity of EAE, demonstrating the importance of MCAM in disease pathogenesis.
“Injection of anti-MCAM antibodies into mice also reduces the severity of EAE, demonstrating the importance of this adhesion molecule in disease pathogenesis (122, 123).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [122]
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CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases
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Endothelial-Specific Deletion of CD146 Protects Against Experimental Glomerulonephritis in Mice
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- Authors
- Duan, H., Xing, S., Luo, Y., Feng, L., Gramaglia, I., Zhang, Y., Lu, D., Zeng, Q., Fan, K., Feng, J., Yang, D., Qin, Z., Couraud, P.-O., Romero, I. A., Weksler, B., & Yan, X.
- Affiliations
- Chinese Academy of Sciences (CN)
- Beijing Anzhen Hospital (CN)
- La Jolla Infectious Disease Institute (US)
- Centre National de la Recherche Scientifique (FR)
- The Open University (GB)
- Weill Cornell Medicine (US)
- Corresponding author
- Yan, Xiyun
- ORCID
- Venue
- Scientific Reports
- Published
- 2013-04-18
- Volume
- 3
- Issue
- 1
- Pages
- 1687-1687
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC3629416
- OpenAlex
- W2014000062
- Cited by
- 59
- References
- 57
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 9 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 9 · 2014: 5
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Open Research Online (The Open University) (submittedVersion)
- Funders
- National Natural Science Foundation of China (973 Program, 91029732, 2011CB915502, 81272409)
- National Key Research and Development Program of China (2011CB915502, 81272409, 2009CB521704)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- CD146, multiple sclerosis, neuroinflammation, lymphocyte extravasation, blood-brain barrier, encephalitogenic T cells, Th1 cells, Th17 cells, leukocyte migration
- MeSH terms
- Animals, Brain, Encephalitis, Endothelium, Vascular, Lymphocytes, Multiple Sclerosis, Mice, Knockout, Mice, CD146 Antigen
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