The Clinicopathologic Significance of Inflammasome Activation in Autoimmune Diseases

AbstractAutoimmune diseases are characterized by dysregulated immune tolerance to self and inflammatory damage to tissues and organs. The development of inflammation involves multiple innate and adaptive immune pathways. Inflammasomes are multimeric cytosolic protein complexes that form to mediate host immune responses upon recognizing pathogen ‐ or danger‐associated molecular patterns via pattern recognition receptors (PRRs). The accelerating pace of inflammasome research has demonstrated important roles for inflammasome activation in many pathologic conditions encompassing infectious, metabolic, autoinflammatory, and autoimmune disea ses. The inflammasome is generally comprised of a PRR, pro‐caspase‐1 and an adaptor molecule connecting the PRR and pro‐caspase‐1. With inflammasome activation, pro‐caspase‐1 becomes active caspase‐1 that converts pro‐IL‐1β and pro‐IL‐18 into mature and active IL‐1β and IL‐ 18, respectively. Having multipotent effects on immune and non‐immune cells, the cytokines IL‐1β and IL‐18 induce and promote systemic and local inflammatory responses. Human studies have reported increased levels of these cytokines, altered activation of inflammasome‐related molecules, and /or presence of inflammasome activators in rheumatic diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), crystal‐induced arthropathies, and Sjögren's syndrome. Such changes are found in the primary target organs lik...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: REVIEW ARTICLE Source Type: research