Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis - Université de Paris - Faculté de Santé Access content directly
Journal Articles (Review Article) Journal of Neuroinflammation Year : 2023

Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis

Abstract

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.
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Dates and versions

hal-03972909 , version 1 (03-02-2023)

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José A Villegas, Jérôme van Wassenhove, Judith Merrheim, Karen Matta, Samy Hamadache, et al.. Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis. Journal of Neuroinflammation, 2023, 20 (1), pp.9. ⟨10.1186/s12974-023-02691-3⟩. ⟨hal-03972909⟩
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