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

J Neuroinflammation. 2023 Jan 13;20(1):9. doi: 10.1186/s12974-023-02691-3.


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.

Keywords: Autoimmunity; Germinal centers; Inflammation; Muscle regeneration; Neuromuscular junction; Th17.

MeSH terms

  • Animals
  • Autoantibodies
  • Humans
  • Interleukin-23 Subunit p19
  • Interleukin-23*
  • Mice
  • Myasthenia Gravis, Autoimmune, Experimental*
  • Neuromuscular Junction / pathology
  • Receptors, Cholinergic


  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Receptors, Cholinergic
  • Autoantibodies