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- Title
Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis.
- Authors
Villegas, José A.; Van Wassenhove, Jérôme; Merrheim, Judith; Matta, Karen; Hamadache, Samy; Flaugère, Clémence; Pothin, Pauline; Truffault, Frédérique; Hascoët, Sébastien; Santelmo, Nicola; Alifano, Marco; Berrih-Aknin, Sonia; le Panse, Rozen; Dragin, Nadine
- Abstract
Acetylcholine receptor (AChR) myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness. The AChR+ autoantibodies are produced by B-cells located in thymic ectopic germinal centers (eGC). No therapeutic approach is curative. The inflammatory IL-23/Th17 pathway is activated in the thymus as well as in the blood and the muscle, contributing to the MG pathogenic events. We aimed to study a potential new therapeutic approach that targets IL-23p19 (IL-23) in the two complementary preclinical MG models: the classical experimental MG mouse model (EAMG) based on active immunization and the humanized mouse model featuring human MG thymuses engrafted in NSG mice (NSG-MG). In both preclinical models, the anti-IL-23 treatment ameliorated MG clinical symptoms. In the EAMG, the treatment reduced IL-17 related inflammation, anti-AChR IgG2b antibody production, activated transduction pathway involved in muscle regeneration and ameliorated the signal transduction at the neuromuscular junction. In the NSG-MG model, the treatment reduced pathogenic Th17 cell population and expression of genes involved in eGC stabilization and B-cell development in human MG thymus biopsies. Altogether, these data suggest that a therapy targeting IL-23p19 may promote significant clinical ameliorations in AChR+ MG disease due to concomitant beneficial effects on the thymus and skeletal muscle defects.
- Subjects
NUCLEAR Suppliers Group (Company); MYASTHENIA gravis; INTERLEUKIN-23; ANTIBODY formation; GERMINAL centers; THERAPEUTICS; MUSCLE weakness
- Publication
Journal of Neuroinflammation, 2023, Vol 20, Issue 1, p1
- ISSN
1742-2094
- Publication type
Article
- DOI
10.1186/s12974-023-02691-3