Clinicopathologic Significance of Inflammasome Activation in Autoimmune Diseases

Autoimmune 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 damage‐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, including infectious, metabolic, autoinflammatory, and autoimmune disea ses. The inflammasome generally comprises a PRR, procaspase 1, and an adaptor molecule connecting the PRR and procaspase 1. Upon inflammasome activation, procaspase 1 becomes active caspase 1 that converts pro–interleukin‐1β (proIL‐1β) and proIL‐18 into mature and active IL‐1β and IL‐ 18, respectively. The cytokines IL‐1β and IL‐18 have multipotent effects on immune and nonimmune cells and induce and promote systemic and local inflammatory responses. Human studies have shown increased levels of these cytokines, altered activation of inflammasome‐related molecules, and/or t he presence of inflammasome activators in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, crystal‐induced arthropathies, and Sjögren's syndrome. Such changes are found in the primary target organs, such as the kidneys, jo...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: ADVANCES IN DISEASE MECHANISMS AND TRANSLATIONAL TECHNOLOGIES Source Type: research