Junctional adhesion molecule-A deficient mice are protected from severe experimental autoimmune encephalomyelitis.
Eur J Immunol
; 54(6): e2350761, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38566526
ABSTRACT
In multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), early pathological features include immune cell infiltration into the central nervous system (CNS) and blood-brain barrier (BBB) disruption. We investigated the role of junctional adhesion molecule-A (JAM-A), a tight junction protein, in active EAE (aEAE) pathogenesis. Our study confirms JAM-A expression at the blood-brain barrier and its luminal redistribution during aEAE. JAM-A deficient (JAM-A-/-) C57BL/6J mice exhibited milder aEAE, unrelated to myelin oligodendrocyte glycoprotein-specific CD4+ T-cell priming. While JAM-A absence influenced macrophage behavior on primary mouse brain microvascular endothelial cells (pMBMECs) under flow in vitro, it did not impact T-cell extravasation across primary mouse brain microvascular endothelial cells. At aEAE onset, we observed reduced lymphocyte and CCR2+ macrophage infiltration into the spinal cord of JAM-A-/- mice compared to control littermates. This correlated with increased CD3+ T-cell accumulation in spinal cord perivascular spaces and brain leptomeninges, suggesting JAM-A absence leads to T-cell trapping in central nervous system border compartments. In summary, JAM-A plays a role in immune cell infiltration and clinical disease progression in aEAE.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Barrera Hematoencefálica
/
Ratones Noqueados
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Células Endoteliales
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Encefalomielitis Autoinmune Experimental
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Macrófagos
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Ratones Endogámicos C57BL
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suiza