Exosomes Regulate NLRP3 Inflammasome in Diseases

Abstract

Emerging evidence has suggested the unique and critical role of exosomes as signal molecules vector in various diseases. Numerous researchers have been trying to identify how these exosomes function in immune progression, as this could promote their use as biomarkers for the disease process and potential promising diagnostic tools. NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3), a tripartite protein, contains three functional domains a central nucleotide-binding and oligomerization domain (NACHT), an N-terminal pyrin domain (PYD), and a leucine-rich repeat domain (LRR). Of note, existing studies have identified exosome as a novel mediator of the NLRP3 inflammasome, which is critical in diseases progression. However, the actual mechanisms and clinical treatment related to exosomes and NLRP3 are still not fully understood. Herein, we presented an up-to-date review of exosomes and NLRP3 in diseases, outlining what is known about the role of exosomes in the activation of NLRP3 inflammasome and also highlighting areas of this topic that warrant further study.

Focus on the Role of the NLRP3 Inflammasome in Multiple Sclerosis: Pathogenesis, Diagnosis, and Therapeutics

“…Research has demonstrated that exosomes/microvesicles from periodontal ligament stem cells of MS patients can inhibit NLRP3 inflammasome activation and attenuate the severity of EAE (Soundara Rajan et al, 2017 ). In detail, the effects of exosomes on NLRP3 inflammasome activation depend on the origin of exosomes, including inhibition (from plasma, mesenchymal stem cells, and macrophages) and promotion (from cancer cells) (Li et al, 2021 ). For example, Yan et al ( 2020 ) reported that exosomes derived from human umbilical cord mesenchymal stem cells could inhibit NLRP3 inflammasome activation by releasing circular RNA homeodomain-interacting protein kinase 3 (circHIPK3).…”

The Role of the NLRP3 Inflammasome in HCC Carcinogenesis and Treatment: Harnessing Innate Immunity

“…The NLRP3 inflammasome has been identified as a mediator in a wide variety of diseases and as a potential novel therapeutic target. Since its role in the progression of atherosclerosis, heart failure, glomerulonephritis and several infectious diseases [25][26][27][28][29] has been acknowledged, it would be useful to highlight the most fundamental stages of NLRP3 activation. It resides in the cytoplasm and acts as an immune sensor to a plethora of stimuli, producing IL-1b and IL-18 and initiating the immune response.…”

“…Their application extends from HCC diagnosis, staging and tumor grading to guiding therapeutic management. Several studies [9] considering the NLRP3 as a biomarker in several malignancies have begun to accumulate [29]. The reduced expression of NLRP3 in colorectal cancer (CRC) tissue holds a positive predictive value [93].…”

The Role of NLRP3 Inflammasome in IgA Nephropathy

“…Emerging evidence has revealed the relationship between exosomes and the NLRP3 inflammasome [ 61 , 62 , 63 , 64 ]. Recent studies have shown that exosomes can influence the course of NLRP3 inflammasome-associated diseases by secreting different substances that affect key molecules in the canonical pathway [ 61 , 62 ].…”