The entrenchment of NLRP3 inflammasomes in autoimmune disease-related inflammation

Abstract

Autoinflammation and autoimmunity are almost “opposite” phenomena characterized by chronic activation of the immune system, ‘innate’ in the first and ‘adaptive’ in the second, leading to inflammation of several tissues with specific protean effectors of tissue damage. The mechanism of involvement of multiprotein complexes called ‘inflammasomes’ within autoimmune pictures, differently from autoinflammatory conditions, is yet undeciphered. In this review we provide a comprehensive overview on NLRP3 inflammasome contribution into the pathogenesis of some autoimmune diseases. In response to autoantibodies against nucleic acids or tissue-specific antigens the NLRP3 inflammasome is activated within dendritic cells and macrophages of patients with systemic lupus erythematosus. Crucial is NLRP3 inflammasome to amplify tissue inflammation with interleukin-1 overexpression and matrix metalloproteinase production at the joint level in rheumatoid arthritis. A deregulated NLRP3 inflammasome activation occurs in the serous acini of salivary and lacrimal glands prone to Sjogren's syndrome, but also in the inflammatory process involving endothelial cells, leucocyte recruitment, and platelet plugging of vasculitides. Furthermore, organ-specific autoimmune diseases such as thyroiditis and hepatitis may display hyperactive NLRP3 inflammasomes at the level of resident immune cells within thyroid or liver, respectively. Therefore, it is not unexpected that preclinical studies have shown how specific inflammasome inhibitors may significantly overthrow the severity of different autoimmune diseases and slow down their trend towards an ominous progression. Specific markers of inflammasome activation could also reveal subclinical inflammatory components escaping conventional diagnostic approaches or improve monitoring of autoimmune diseases and personalizing their treatment.