Abstract
The NLRP3 (nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome is a protein complex expressed in cells. It detects danger signals and induces the production of active caspase-1 and the maturation and release of IL (interleukin)-33, IL-18, IL-1β and other cytokines. T1DM (type 1 diabetes mellitus) is defined as a chronic autoimmune disorder characterized by the autoreactive T cell-mediated elimination of insulin-positive pancreatic beta-cells. Although the exact underlying mechanisms are obscure, researchers have proposed that both environmental and genetic factors are involved in the pathogenesis of T1DM. Furthermore, immune responses, including innate and adaptive immunity, play an important role in this process. Recently, the NLRP3 inflammasome, a critical component of innate immunity, was reported to be associated with T1DM. Here, we review the assembly and function of the NLRP3 inflammasome. In addition, the activation and regulatory mechanisms that enhance or attenuate NLRP3 inflammasome activation are discussed. Finally, we focus on the relationship between the NLRP3 inflammasome and T1DM, as well as its potential value for clinical use.
Highlights
The inflammatory response is a common mechanism of many diseases
The levels of IL-1 receptor antagonist (IL-1RA), which inhibits the interaction between IL-1β and its receptor and blocks downstream signaling, are decreased in islets from non-diabetic donors exposed to sera from patients with T1DM, and decreased expression of IL1RA results in insulin-producing beta-cell dysfunction and death and IL-1β production, further affecting beta-cells [109]
The discovery of the NLRP3 inflammasome has provided a new opportunity to explore the pathogenesis of inflammation-related diseases
Summary
The inflammatory response is a common mechanism of many diseases. the clinical manifestations caused by the combination of a certain microenvironment and a variety of stimuli from common or specific pathways are different. The levels of IL-1 receptor antagonist (IL-1RA), which inhibits the interaction between IL-1β and its receptor and blocks downstream signaling, are decreased in islets from non-diabetic donors exposed to sera from patients with T1DM, and decreased expression of IL1RA results in insulin-producing beta-cell dysfunction and death and IL-1β production, further affecting beta-cells [109]. The expression of the NLRP3 inflammasome is downregulated in patients with SLE compared with healthy controls and is negatively correlated with disease activity, indicating a protective effect of the inflammasome on SLE [122] Consistent with these findings, another study examining T1DM indicated that downregulated NLRP3 inflammasome signaling participates in the early stage of autoimmune diabetes [123]. A better understanding of the NLRP3 inflammasome is still needed to completely ascertain its effect on the pathogenesis of T1DM and develop new treatment strategies
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