Melanoma cell adhesion molecule identifies encephalitogenic T lymphocytes and promotes their recruitment to the central nervous system
Abstract
In multiple sclerosis, encephalitogenic CD4(+) lymphocytes require adhesion molecules to accumulate into central nervous system inflammatory lesions. Using proteomic techniques, we identified expression of melanoma cell adhesion molecule (MCAM) on a subset of human effector memory CD4(+) lymphocytes and on human blood-brain barrier endothelium. Herein, we demonstrate that MCAM is a stable surface marker that refines the identification of interleukin 17(+), interleukin 22(+), RAR-related orphan receptor γ and interleukin 23 receptor(+) cells within the CD161(+)CCR6(+) subset of memory CD4(+) lymphocytes. We also show that MCAM(+) lymphocytes express significantly more granulocyte/macrophage colony stimulating factor and granzyme B than MCAM(-) lymphocytes. Furthermore, the proportion of MCAM(+) CD4(+) lymphocytes is significantly increased in the blood and in the central nervous system of patients with multiple sclerosis and experimental autoimmune encephalomyelitis animals compared with healthy controls or other neurological diseases, and MCAM expression is upregulated at the blood-brain barrier within inflammatory lesions. Moreover, blockade of MCAM or depletion of MCAM(+) CD4(+) T lymphocytes both restrict the migration of T(H)17 lymphocytes across blood-brain barrier endothelial cells and decrease the severity of experimental autoimmune encephalomyelitis. Our findings indicate that MCAM could serve as a potential biomarker for multiple sclerosis and represents a valuable target for the treatment of neuroinflammatory conditions.
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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 [123]
MCAM+ effector T cells migrate more efficiently across the BBB than MCAM-negative counterparts through homotypic binding with MCAM on vascular endothelial cells and interactions with laminin-411.
“MCAM+ effector T cells migrate more efficiently across the BBB than their MCAM-negative counterparts and appear to do so through homotypic binding with MCAM expressed on vascular endothelial cells (123) and through interactions with laminin-411 (124).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [123]
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 [123]
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- Authors
- Larochelle, C., Cayrol, R., Kebir, H., Alvarez, J. I., Lécuyer, M.-A., Ifergan, I., Viel, É., Bourbonnière, L., Beauseigle, D., Terouz, S., Hachehouche, L., Gendron, S., Poirier, J., Jobin, C., Duquette, P., Flanagan, K., Yednock, T., Arbour, N., & Prat, A.
- Affiliations
- Hôpital Notre-Dame (CA)
- Centre Hospitalier de l’Université de Montréal (CA)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-09-13
- Volume
- 135
- Issue
- 10
- Pages
- 2906-2924
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2079937854
- Cited by
- 145
- References
- 61
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 9 · 2023: 9 · 2022: 14 · 2021: 8 · 2020: 9 · 2019: 15 · 2018: 7 · 2017: 10 · 2016: 8 · 2015: 25 · 2014: 10 · 2013: 8 · 2012: 1
- FWCI
- 10.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- CD146, multiple sclerosis, experimental autoimmune encephalomyelitis, CD4+ T cells, Th17 cells, effector memory T cells, blood-brain barrier, T cell migration, CCR6, CD161, IL-17, IL-22, RORγt, IL23R, granulocyte colony-stimulating factor, granzyme B, biomarkers, neuroinflammation
- MeSH terms
- Animals, Cell Movement, Cells, Cultured, Central Nervous System, Encephalomyelitis, Autoimmune, Experimental, Humans, Mice, Inbred C57BL, Multiple Sclerosis, Biomarkers, Neurogenic Inflammation, Mice, CD146 Antigen
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