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001     283126
005     20260218110648.0
024 7 _ |a 10.1038/s41590-025-02359-5
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024 7 _ |a 1529-2908
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024 7 _ |a 1529-2916
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037 _ _ |a DZNE-2026-00022
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Naouar, Ikbel
|b 0
245 _ _ |a Lymphotoxin-dependent elevated meningeal CXCL13:BAFF ratios drive gray matter injury.
260 _ _ |a London
|c 2026
|b Springer Nature Limited
336 7 _ |a article
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520 _ _ |a In multiple sclerosis (MS), B cell-rich tertiary lymphoid tissues (TLTs) in the brain leptomeninges associate with cortical gray matter injury. Using a model of Th17 cell-driven experimental autoimmune encephalomyelitis in mice, we found that inhibitors of Bruton's tyrosine kinase (BTKi) prevented TLT formation and cortical pathology in a B cell activating factor (BAFF)-dependent manner. BTKi reduced expression of lymphotoxin ligands, and cotreatment with a lymphotoxin-β receptor agonist abrogated the benefits of BTKi. TLT and cortical pathology tracked with a high CXCL13:BAFF ratio in the leptomeninges, which was reduced by BTKi. Moreover, we observed high CXCL13:BAFF ratios in post mortem cerebral spinal fluid from patients with MS and pathologically confirmed leptomeningeal inflammation, as well as in living patients with MS and radiologically confirmed paramagnetic rim lesions. In summary, using experimental autoimmune encephalomyelitis, we revealed a molecular circuit that leads to TLT formation and cortical injury with translational relevance for detection of this pathology in patients with MS.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
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650 _ 7 |a Chemokine CXCL13
|2 NLM Chemicals
650 _ 7 |a B-Cell Activating Factor
|2 NLM Chemicals
650 _ 7 |a CXCL13 protein, human
|2 NLM Chemicals
650 _ 7 |a Lymphotoxin-alpha
|2 NLM Chemicals
650 _ 7 |a Cxcl13 protein, mouse
|2 NLM Chemicals
650 _ 7 |a TNFSF13B protein, human
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Chemokine CXCL13: metabolism
|2 MeSH
650 _ 2 |a Chemokine CXCL13: immunology
|2 MeSH
650 _ 2 |a Gray Matter: immunology
|2 MeSH
650 _ 2 |a Gray Matter: pathology
|2 MeSH
650 _ 2 |a Gray Matter: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Encephalomyelitis, Autoimmune, Experimental: immunology
|2 MeSH
650 _ 2 |a Encephalomyelitis, Autoimmune, Experimental: pathology
|2 MeSH
650 _ 2 |a Meninges: immunology
|2 MeSH
650 _ 2 |a Meninges: metabolism
|2 MeSH
650 _ 2 |a Meninges: pathology
|2 MeSH
650 _ 2 |a B-Cell Activating Factor: metabolism
|2 MeSH
650 _ 2 |a B-Cell Activating Factor: immunology
|2 MeSH
650 _ 2 |a Multiple Sclerosis: immunology
|2 MeSH
650 _ 2 |a Multiple Sclerosis: pathology
|2 MeSH
650 _ 2 |a Multiple Sclerosis: metabolism
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Lymphotoxin-alpha: metabolism
|2 MeSH
650 _ 2 |a Th17 Cells: immunology
|2 MeSH
650 _ 2 |a Tertiary Lymphoid Structures: immunology
|2 MeSH
650 _ 2 |a Tertiary Lymphoid Structures: pathology
|2 MeSH
650 _ 2 |a B-Lymphocytes: immunology
|2 MeSH
700 1 _ |a Pangan, Andrei
|b 1
700 1 _ |a Zuo, Michelle
|0 0000-0002-6704-453X
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700 1 _ |a Raza, Syed Ali
|0 0000-0003-4782-2100
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700 1 _ |a Champagne-Jorgensen, Kevin
|0 0000-0002-1445-1449
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700 1 _ |a Patel, Jyot
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700 1 _ |a Wang, Angela
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700 1 _ |a Pu, Annie
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700 1 _ |a Ward, Lesley
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700 1 _ |a Ahn, Jennifer S Y
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700 1 _ |a Sayeed, Faizah N
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700 1 _ |a Zhu, Jingwen
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700 1 _ |a Pössnecker, Elisabeth
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700 1 _ |a Spring, Shoshana
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700 1 _ |a Sled, John G
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700 1 _ |a Cenni, Bruno
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700 1 _ |a Nuesslein-Hildesheim, Barbara
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700 1 _ |a Browning, Jeffrey L
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700 1 _ |a Pröbstel, Anne-Katrin
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700 1 _ |a Reich, Daniel S
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700 1 _ |a Gommerman, Jennifer L
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700 1 _ |a Ramaglia, Valeria
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773 _ _ |a 10.1038/s41590-025-02359-5
|g Vol. 27, no. 1, p. 48 - 60
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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