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000283126 1001_ $$aNaouar, Ikbel$$b0
000283126 245__ $$aLymphotoxin-dependent elevated meningeal CXCL13:BAFF ratios drive gray matter injury.
000283126 260__ $$aLondon$$bSpringer Nature Limited$$c2026
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000283126 520__ $$aIn multiple sclerosis (MS), B cell-rich tertiary lymphoid tissues (TLTs) in the brain leptomeninges associate with cortical gray matter injury. Using a model of Th17 cell-driven experimental autoimmune encephalomyelitis in mice, we found that inhibitors of Bruton's tyrosine kinase (BTKi) prevented TLT formation and cortical pathology in a B cell activating factor (BAFF)-dependent manner. BTKi reduced expression of lymphotoxin ligands, and cotreatment with a lymphotoxin-β receptor agonist abrogated the benefits of BTKi. TLT and cortical pathology tracked with a high CXCL13:BAFF ratio in the leptomeninges, which was reduced by BTKi. Moreover, we observed high CXCL13:BAFF ratios in post mortem cerebral spinal fluid from patients with MS and pathologically confirmed leptomeningeal inflammation, as well as in living patients with MS and radiologically confirmed paramagnetic rim lesions. In summary, using experimental autoimmune encephalomyelitis, we revealed a molecular circuit that leads to TLT formation and cortical injury with translational relevance for detection of this pathology in patients with MS.
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000283126 650_7 $$2NLM Chemicals$$aChemokine CXCL13
000283126 650_7 $$2NLM Chemicals$$aB-Cell Activating Factor
000283126 650_7 $$2NLM Chemicals$$aCXCL13 protein, human
000283126 650_7 $$2NLM Chemicals$$aLymphotoxin-alpha
000283126 650_7 $$2NLM Chemicals$$aCxcl13 protein, mouse
000283126 650_7 $$2NLM Chemicals$$aTNFSF13B protein, human
000283126 650_2 $$2MeSH$$aAnimals
000283126 650_2 $$2MeSH$$aChemokine CXCL13: metabolism
000283126 650_2 $$2MeSH$$aChemokine CXCL13: immunology
000283126 650_2 $$2MeSH$$aGray Matter: immunology
000283126 650_2 $$2MeSH$$aGray Matter: pathology
000283126 650_2 $$2MeSH$$aGray Matter: metabolism
000283126 650_2 $$2MeSH$$aHumans
000283126 650_2 $$2MeSH$$aMice
000283126 650_2 $$2MeSH$$aEncephalomyelitis, Autoimmune, Experimental: immunology
000283126 650_2 $$2MeSH$$aEncephalomyelitis, Autoimmune, Experimental: pathology
000283126 650_2 $$2MeSH$$aMeninges: immunology
000283126 650_2 $$2MeSH$$aMeninges: metabolism
000283126 650_2 $$2MeSH$$aMeninges: pathology
000283126 650_2 $$2MeSH$$aB-Cell Activating Factor: metabolism
000283126 650_2 $$2MeSH$$aB-Cell Activating Factor: immunology
000283126 650_2 $$2MeSH$$aMultiple Sclerosis: immunology
000283126 650_2 $$2MeSH$$aMultiple Sclerosis: pathology
000283126 650_2 $$2MeSH$$aMultiple Sclerosis: metabolism
000283126 650_2 $$2MeSH$$aFemale
000283126 650_2 $$2MeSH$$aMale
000283126 650_2 $$2MeSH$$aMice, Inbred C57BL
000283126 650_2 $$2MeSH$$aLymphotoxin-alpha: metabolism
000283126 650_2 $$2MeSH$$aTh17 Cells: immunology
000283126 650_2 $$2MeSH$$aTertiary Lymphoid Structures: immunology
000283126 650_2 $$2MeSH$$aTertiary Lymphoid Structures: pathology
000283126 650_2 $$2MeSH$$aB-Lymphocytes: immunology
000283126 7001_ $$aPangan, Andrei$$b1
000283126 7001_ $$00000-0002-6704-453X$$aZuo, Michelle$$b2
000283126 7001_ $$00000-0003-4782-2100$$aRaza, Syed Ali$$b3
000283126 7001_ $$00000-0002-1445-1449$$aChampagne-Jorgensen, Kevin$$b4
000283126 7001_ $$00009-0002-0838-7206$$aPatel, Jyot$$b5
000283126 7001_ $$00000-0001-6991-7368$$aWang, Angela$$b6
000283126 7001_ $$aPu, Annie$$b7
000283126 7001_ $$aWard, Lesley$$b8
000283126 7001_ $$00009-0005-5305-8956$$aAhn, Jennifer S Y$$b9
000283126 7001_ $$aSayeed, Faizah N$$b10
000283126 7001_ $$aZhu, Jingwen$$b11
000283126 7001_ $$00000-0002-6271-2404$$aPössnecker, Elisabeth$$b12
000283126 7001_ $$aSpring, Shoshana$$b13
000283126 7001_ $$aSled, John G$$b14
000283126 7001_ $$00000-0002-8603-2032$$aCenni, Bruno$$b15
000283126 7001_ $$aNuesslein-Hildesheim, Barbara$$b16
000283126 7001_ $$00000-0001-9168-5233$$aBrowning, Jeffrey L$$b17
000283126 7001_ $$0P:(DE-2719)9003515$$aPröbstel, Anne-Katrin$$b18
000283126 7001_ $$00000-0002-2628-4334$$aReich, Daniel S$$b19
000283126 7001_ $$00000-0003-4576-6168$$aGommerman, Jennifer L$$b20
000283126 7001_ $$00000-0002-9401-5988$$aRamaglia, Valeria$$b21
000283126 773__ $$0PERI:(DE-600)2026412-4$$a10.1038/s41590-025-02359-5$$gVol. 27, no. 1, p. 48 - 60$$n1$$p48 - 60$$tNature immunology$$v27$$x1529-2908$$y2026
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