In fact, above responses have been identified to be involved in the development of autoimmunity, specifically, the NLRP3 inflammasome could promote inflammation in massive autoimmune diseases and TG2, as well as cathepsin may contribute to joint destruction and degeneration in inflammatory arthritis.
The NLRP3 inflammasome is associated with the onset and progression of autoinflammatory and autoimmune diseases, including metabolic disorders, multiple sclerosis, inflammatory bowel disease, and cryopyrin-associated periodic fever syndrome.
The NLRP3 inflammasome has been associated with several human inflammatory and autoimmune diseases and represents a potential therapeutic target for disrupting IL-1β production.
Genetic polymorphisms in genes coding for inflammasome components <i>nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3)</i> and <i>caspase recruitment domain-containing protein 8 (CARD8)</i> have been associated with autoinflammatory and autoimmune diseases.
In this review, we will briefly discuss the biological features of NLRP3 and summarize the recent progression of the involvement of NLRP3 in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.
The NLRP3 inflammasome must be well orchestrated to prevent the aberrant activations under physiological and pathological conditions, because uncontrolled activation of NLRP3 inflammasome is one of the major causes of a variety of autoimmune diseases and metabolic disorders.
A comprehensive understanding of mitochondrial role in toll-like receptor-mediated innate immune responses and NLRP3 inflammasome complex activation, will facilitate development of novel therapeutics to treat various infectious, inflammatory, and autoimmune disorders.
The Nod-like receptor pyrin containing 3 inflammasome (NLRP3) is an intracellular multiprotein complex responsible for a number of innate immune processes associated with infection, inflammation and autoimmunity.
Although the importance of the NACHT, LRR and PYD domains-containing protein 3 (NALP3) inflammasome as the initial immune reaction against silica particles has been identified, the mechanisms involved that lead to various autoimmune diseases in patients exposed to silica remain largely unknown.
An ever increasing number of studies link the sensing of cellular stress signals to a direct pathophysiological role of NLRP3 activation in a wide range of autoinflammatory and autoimmune disorders, and thus provide a novel mechanistic rational, on how molecules trigger and support sterile inflammatory diseases.
Moreover, stratifying patients according to the presence of rheumatoid factor (RF), anti-cyclic peptides antibodies (ACPA), erosion, nodules, other autoimmune disease or HLA-DRB1*04-positive subgroups did not show any significant association with CARD8 or NLRP3 (P ≥ 0.05).
Since it has been reported that IL-1 beta has a systemic effect in the lost of the immunologic tolerance and that NALP3 inflammasome is directly involved in the production of this pro-inflammatory cytokine, we hypothesized that variations in NLRP3 could belong to a predisposing genetic background that contribute to the development of autoimmune diseases.
Although the role of NLRP3 in host response to pathogen associated molecular patterns and danger associated molecular patterns is well documented, its role in autoimmune diseases is less well studied.