Progress in the relationship of A20 and NLRP3 inflammasome with juvenile idiopathic arthritis / 中华微生物学和免疫学杂志

ABSTRACT

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases characterized by chronic inflammatory arthritis of unknown cause, lasting six weeks or longer, and accompanied by organ damages. It is the most common chronic inflammatory rheumatic disease in childhood with unclear aetiology. A20, a protein encoded by the tumor necrosis factor α-induced protein 3 gene (TNFAIP3), regulates cell inflammatory response and apoptosis through suppressing inflammatory NF-κB signaling by acting as an ubiquitin-editing enzyme. NOD-like receptor protein 3 (NLRP3) inflammasome, a multiprotein complex formed by a subgroup of intracellular pattern recognition receptors, mediates the activation of caspase-1 and the secretion of proinflammatory cytokines IL-1β and IL-18 in response to microbial infection and cellular damage. A20 could directly reduce the basal expression of NLRP3 to impair caspase-1 activation and inhibit the assembling of NLRP3 inflammasome by suppressing the activation of NF-κB, playing a crucial anti-inflammatory role in JIA. A20 and NLRP3 inflammasome may be promising prognostic markers and therapeutic targets in JIA. This review summarized the structure and biological function of A20 and NLRP3 inflammasome and analyzed their roles in the genetic susceptibility and pathogenesis of JIA.