NLRP3 Inflammasome: Checkpoint Connecting Innate and Adaptive Immunity in Autoimmune Diseases

Abstract

Autoimmune diseases are a broad spectrum of human diseases that are characterized by the breakdown of immune tolerance and the production of autoantibodies. Recently, dysfunction of innate and adaptive immunity is considered to be a key step in the initiation and maintenance of autoimmune diseases. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a multimeric protein complex, which can detect exogenous pathogen irritants and endogenous danger signals. The main function of NLRP3 inflammasome is to promote secretion of interleukin (IL)-1β and IL-18, and pyroptosis mediated by caspase-1. Served as a checkpoint in innate and adaptive immunity, aberrant activation and regulation of NLRP3 inflammasome plays an important role in the pathogenesis of autoimmune diseases. This paper reviewed the roles of NLRP3 inflammasome in autoimmune diseases, which shows NLRP3 inflammasome may be a potential target for autoimmune diseases deserved further study.

Role of NLRP3 Inflammasome in Rheumatoid Arthritis

“…Hence, the regulation of its activation process is quite complex. Some potential regulatory mechanisms have been studied, such as the role of NIMA-related kinase 7 (NEK7), the regulation of autophagy/mTOR pathway, and changes in subcellular localization ( 27 , 33 , 34 ).…”

“…The pathogenic role of NLRP3 has been demonstrated in systemic lupus erythematosus, inflammatory bowel disease, and type 1 diabetes mellitus(T1DM). Nevertheless, the protective effect of NLRP3 inflammasome has also been illustrated in these diseases ( 34 ). The exact mechanism of this effect is not specified, requiring a deeper understanding of the role of NLRP3 inflammasome in diseases.…”

The First Approved COVID-19 Vaccines: The Road to Cancer Vaccines

“…However, any defect in either innate or adaptive system can lead to immunopathological disorders such as autoimmune diseases [22]. From this perspective, adaptive immunity could also damage healthy tissues if it is directed to an undesirable target such as self-protein, as it occurs in autoimmune diseases [23]. It is consistent across many studies that the adaptive response has memory, which means that further exposure leads to a more determined and faster response [20].…”

The Role of NLRP3 Inflammasome in Diabetic Cardiomyopathy and Its Therapeutic Implications

“…NLRP3 inflammasome activation necessitates two sequential procedures, namely, priming and assembly. In the priming phase, pattern recognition receptors, TNF receptors, and IL-1 receptors recognize the corresponding priming signals (including pathogen-associated molecular patterns, damage-associated molecular patterns, TNF- α , and IL-1 β ), thereby promoting NF- κ B transcription and enhancing the production of NLRP3, pro-IL-1 β , and pro-IL-18 [ 35 , 36 ]. Sequentially, NLRP3 undergoes posttranslational modifications (PTMs) and binds to NIMA-related kinase 7 (Nek7) to form the NLRP3-Nek7 complex, which becomes activated.…”