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@ARTICLE{Naouar:283126,
author = {Naouar, Ikbel and Pangan, Andrei and Zuo, Michelle and
Raza, Syed Ali and Champagne-Jorgensen, Kevin and Patel,
Jyot and Wang, Angela and Pu, Annie and Ward, Lesley and
Ahn, Jennifer S Y and Sayeed, Faizah N and Zhu, Jingwen and
Pössnecker, Elisabeth and Spring, Shoshana and Sled, John G
and Cenni, Bruno and Nuesslein-Hildesheim, Barbara and
Browning, Jeffrey L and Pröbstel, Anne-Katrin and Reich,
Daniel S and Gommerman, Jennifer L and Ramaglia, Valeria},
title = {{L}ymphotoxin-dependent elevated meningeal {CXCL}13:{BAFF}
ratios drive gray matter injury.},
journal = {Nature immunology},
volume = {27},
number = {1},
issn = {1529-2908},
address = {London},
publisher = {Springer Nature Limited},
reportid = {DZNE-2026-00022},
pages = {48 - 60},
year = {2026},
abstract = {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.},
keywords = {Animals / Chemokine CXCL13: metabolism / Chemokine CXCL13:
immunology / Gray Matter: immunology / Gray Matter:
pathology / Gray Matter: metabolism / Humans / Mice /
Encephalomyelitis, Autoimmune, Experimental: immunology /
Encephalomyelitis, Autoimmune, Experimental: pathology /
Meninges: immunology / Meninges: metabolism / Meninges:
pathology / B-Cell Activating Factor: metabolism / B-Cell
Activating Factor: immunology / Multiple Sclerosis:
immunology / Multiple Sclerosis: pathology / Multiple
Sclerosis: metabolism / Female / Male / Mice, Inbred C57BL /
Lymphotoxin-alpha: metabolism / Th17 Cells: immunology /
Tertiary Lymphoid Structures: immunology / Tertiary Lymphoid
Structures: pathology / B-Lymphocytes: immunology /
Chemokine CXCL13 (NLM Chemicals) / B-Cell Activating Factor
(NLM Chemicals) / CXCL13 protein, human (NLM Chemicals) /
Lymphotoxin-alpha (NLM Chemicals) / Cxcl13 protein, mouse
(NLM Chemicals) / TNFSF13B protein, human (NLM Chemicals)},
cin = {AG Pröbstel},
ddc = {610},
cid = {I:(DE-2719)1013045},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41482555},
doi = {10.1038/s41590-025-02359-5},
url = {https://pub.dzne.de/record/283126},
}