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. 2024 Jun;54(6):e2350761.
doi: 10.1002/eji.202350761. Epub 2024 Apr 2.

Junctional adhesion molecule-A deficient mice are protected from severe experimental autoimmune encephalomyelitis

Kristina Berve  1 , Julia Michel  1 , Silvia Tietz  1 , Claudia Blatti  1 , Daniela Ivan  1 , Gaby Enzmann  1 , Ruth Lyck  1 , Urban Deutsch  1 , Giuseppe Locatelli  1 , Britta Engelhardt  1
Affiliations

Junctional adhesion molecule-A deficient mice are protected from severe experimental autoimmune encephalomyelitis

Kristina Berve et al. Eur J Immunol. 2024 Jun.

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.

Keywords: Blood–brain barrier; Experimental autoimmune encephalomyelitis; Junctional adhesion molecule A; Macrophages; T cells.

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