Journal of Neuroimmunology · Nov 2026
Urolithin A ameliorates experimental autoimmune myasthenia gravisin association with mitochondrial quality control–related and inflammasome signaling changes
By Zhang N, Kong X, Yu S et al.
Objective To characterize peripheral blood mononuclear cell (PBMC) remodeling in myasthenia gravis (MG) at the pathway and transcriptomic level, and to evaluate whether urolithin A (UA) ameliorates experimental autoimmune myasthenia gravis (EAMG) in association with altered mitochondrial quality control–related and NLRP3 inflammasome signaling. Methods Single-cell RNA-sequencing data from two patients with stable MG and two with MC were analyzed. After quality control, 8414 stable-MG cells and 19,333 MC cells were retained. Cell composition, pathway scores, pseudobulk differential expression, gene-set enrichment, and ligand–receptor interactions were assessed. In parallel, EAMG rats were assigned to control, EAMG, EAMG+UA, or EAMG+UA + chloroquine groups (n = 6/group). Clinical, serological, inflammatory, ultrastructural, mitochondrial quality control–related, and inflammasome-related outcomes were evaluated. Results MC samples showed heterogeneous immune remodeling, including monocyte enrichment in one patient. Across immune-cell subsets, MC was associated with increased inflammatory, inflammasome/pyroptosis, oxidative-stress, chemotaxis, and lysosome–autophagy programs, whereas mitochondrial quality control–related changes were weaker and cell-type dependent. Exploratory analysis suggested enhanced TNFSF13B–TNFRSF13C interaction scores toward B-cell subsets. In EAMG rats, UA reduced clinical weakness, anti-acetylcholine receptor antibodies, and pro-inflammatory cytokines; improved splenic mitochondrial ultrastructure and PINK1/Parkin-associated mitochondrial quality control marker profiles; and suppressed NLRP3/caspase-1/GSDMD-N signaling. Chloroquine partially reversed these effects. Conclusion Exploratory scRNA-seq analysis of four patients suggests that MC is associated with pathway-level enrichment of inflammasome/pyroptosis and autophagy/lysosome programs, whereas mitochondrial quality control–related signals were weaker and cell-type-dependent. The EAMG findings support an association between UA treatment, improved mitochondrial quality control–related marker profiles, and reduced inflammasome activation.