[Regulatory mechanisms of post-translational modifications in inflammasome signaling: a review]

Inflammasomes are central platforms of innate immunity that sense pathogenic and damage-associated signals and drive the maturation of proinflammatory cytokines as well as pyroptotic cell death. Their aberrant activation contributes to a wide range of pathological conditions, including inflammatory, autoimmune, metabolic, and neurological diseases. Recent studies have uncovered a dynamic regulatory network of post-translational modifications (PTMs) that governs the priming, assembly, activation, and degradation of inflammasome signaling. Ubiquitination and deubiquitination primarily control the stability, complex assembly, and degradation of inflammasome components. Phosphorylation and dephosphorylation regulate NLRP3 conformational switching, its interaction with NIMA-related kinase 7, and ASC speck formation through kinase-phosphatase crosstalk, while also modulating NLRC4 and Pyrin inflammasome activation. Acetylation and deacetylation, SUMOylation and deSUMOylation affect inflammasome assembly, protein degradation, and pyroptotic execution in a site- or isoform-specific manner. Collectively, these PTM networks determine the maturation and release of IL-1β and IL-18, as well as the intensity of gasdermin D-mediated pyroptosis. This review summarizes the major types of PTMs, their regulatory mechanisms, and the disease-related advances involving key inflammasome components. It also discusses therapeutic strategies and translational challenges associated with targeting these modification networks, with the aim of providing a reference for mechanistic studies and precision interventions in inflammation-associated diseases.