Differential Expression of NLRP3 among Hematopoietic Cells

Abstract

Although the importance of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in health and disease is well appreciated, a precise characterization of NLRP3 expression is yet undetermined. To this purpose, we generated a knock-in mouse in which the Nlrp3 coding sequence was substituted for the GFP (enhanced GFP [egfp]) gene. In this way, the expression of eGFP is driven by the endogenous regulatory elements of the Nlrp3 gene. In this study, we show that eGFP expression indeed mirrors that of NLRP3. Interestingly, splenic neutrophils, macrophages, and, in particular, monocytes and conventional dendritic cells showed robust eGFP fluorescence, whereas lymphoid subsets, eosinophils, and plasmacytoid dendritic cells showed negligible eGFP levels. NLRP3 expression was highly inducible in macrophages, both by MyD88- and Trif-dependent pathways. In vivo, when mice were challenged with diverse inflammatory stimuli, differences in both the number of eGFP-expressing cells and fluorescence intensity were observed in the draining lymph node. Thus, NLRP3 levels at the site of adaptive response initiation are controlled by recruitment of NLRP3-expressing cells and by NLRP3 induction.

Cutting Edge: miR-223 and EBV miR-BART15 Regulate the NLRP3 Inflammasome and IL-1β Production

“…1B). These data would also agree with the expression pattern of NLRP3-GFP mice where GFP under the Nlrp3 promoter is a surrogate marker or NLRP3 expression, but not regulated by the Nlrp3 39-UTR (5). In that case, NLRP3-GFP protein expression is very high in monocytes, which corresponds to high NLRP3 mRNA levels in our study.…”

NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets

“…NLRP3 is expressed in both immune cells and tissue cells (23,24). To further investigate whether deficiency of NLRP3 in the hematopoietic or nonhematopoietic cell compartment was responsible for the observed protective effect, we performed a set of bone marrow chimera (BMC) experiments.…”

Molecular mechanisms regulating NLRP3 inflammasome activation

“…The first signal in inflammasome activation involves the priming signal, induced by the toll-like receptor (TLR)/nuclear factor (NF)-kB pathway, to upregulate the expression of NLRP3, the level of which is otherwise relatively low in numerous cell types. 5,6 Signal 2 is transduced by various pathogenassociated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) to activate the functional NLRP3 inflammasome by initiating assembly of a multi-protein complex consisting of NLRP3, the adaptor protein ASC, and procaspase-1. Several molecular mechanisms have been suggested for NLRP3 activation to induce caspase-1 activation and IL-1b maturation.…”