Berve, Kristina; Michel, Julia; Tietz, Silvia; Blatti, Claudia; Ivan, Daniela; Enzmann, Gaby; Lyck, Ruth; Deutsch, Urban; Locatelli, Giuseppe; Engelhardt, Britta (2024). Junctional adhesion molecule-A deficient mice are protected from severe experimental autoimmune encephalomyelitis. European journal of immunology, 54(6), e2350761. Wiley-VCH 10.1002/eji.202350761
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Berve, Kristina Carolin, Tietz, Silvia Martina, Blatti, Claudia, Condeescu-Ivan, Daniela, Enzmann, Gaby, Lyck, Ruth, Deutsch, Urban, Locatelli, Giuseppe, Engelhardt, Britta |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0014-2980 |
Publisher: |
Wiley-VCH |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
03 Apr 2024 15:56 |
Last Modified: |
08 Jun 2024 00:14 |
Publisher DOI: |
10.1002/eji.202350761 |
PubMed ID: |
38566526 |
Uncontrolled Keywords: |
Blood–brain barrier Experimental autoimmune encephalomyelitis Junctional adhesion molecule A Macrophages T cells |
BORIS DOI: |
10.48350/195637 |
URI: |
https://boris.unibe.ch/id/eprint/195637 |