Beyond the innate immune system: rethinking in flammasomes in multiple sclerosis

Abstract

Inflammasomes have emerged as central regulators of (auto)immune pathology, including multiple sclerosis (MS). Once exclusively considered in the domain of myeloid cells, both canonical and noncanonical inflammasomes are now recognized in diverse immune and nonimmune populations relevant to MS, including T lymphocytes, blood-brain barrier (BBB) endothelial cells (EnC), and oligodendrocytes (ODCs). Elevated inflammasome activity is evident in patient-derived samples, particularly within active brain lesions. Experimental autoimmune encephalomyelitis (EAE) models confirm the pathogenic contribution of inflammasomes, as genetic deletion or pharmacological inhibition of inflammasomes mitigate disease. These advances position inflammasomes at the intersection of neuroinflammation and neurodegeneration, and highlight inflammasome inhibition as a promising therapeutic avenue currently under investigation in preclinical and early clinical studies.