The genomic actions of VD are mediated by the VDR [9,10]. The VDR is a member of the steroid hormone nuclear receptor family that acts as a transcription factor when activated. VDR has three domains, a C-terminal ligand binding domain for VD binding, an N-terminal DNA binding domain that binds to VD response elements (VDREs) in the promoter region of VD-regulated genes, and a hinge region that binds these domains together [9,10]. The VDR generally interacts with a heterodimer partner retinoid-X receptor (RXR) and coactivators/coregulators, increasing translational activity at a range of target genes that allow for multiple and varied responses across different cell types [2,9,10].  
Figure 1: The process of Vitamin D\({}_{2}\) and D\({}_{3}\) production and activation. 7 dehydrocholesterol is converted to pre-Vitamin D\({}_{3}\) in a UV-B-dependent manner in the skin. Pre-Vitamin D\({}_{3}\) spontaneously isomerises to Vitamin D\({}_{3}\), which is then converted to 25(OH)-Vitamin D\({}_{3}\) by 25-hydroxylase (primarily CYP2R1) in the liver. The final activation step occurs in the kidney, where 1-hydroxylase (CYP27B1, CYP27A1) creates 1,25(OH)-Vitamin D\({}_{3}\). Vitamin D\({}_{2}\) is created from ergosterol in a UV-B-dependent manner in fungi. Following oral consumption, Vitamin D\({}_{2}\) undergoes similar activating processes by 25-hydroxylase (CYP2R1) and 1-hydroxylase (CYP27B1). UV-B: ultraviolet B light. CYP—cytochrome P450 enzyme.  
1,25(OH)\({}_{2}\)-VD\({}_{2}\) and VD\({}_{3}\) also exert rapid non-genomic actions via multiple second messenger pathways [11; 12]. These appear to be mediated by both the nuclear VDR, as well as a membrane-bound receptor known as membrane-associated rapid response steroid binding protein (MARRS) [12; 13]. These non-genomic actions are of interest as they appear to be implicated in many of the immunomodulatory effects of VD.  
Despite the critical role VD plays in health, VD deficiency (VDD) is a common problem worldwide. While definitions are controversial, VDD is generally defined as circulating levels of 25(OH)-VD below 50 nmol/L (\(<\)20 ng/mL) [14]. Reported frequencies in some populations are as high as 90% [15; 16]. This is concerning given the wide range of physiological actions that appear to be influenced by VD, in particular our evolving understanding of the role of VD in moderating immune function.  
VD has a complex role in immune response regulation, both enhancing and suppressing different responses [17]. Emerging evidence suggests a role for VD in modulating inflammation via the inflammasome cascade [18; 19; 20]. Part of the innate immune system, inflammasomes are large, multimeric protein complexes that assemble in the cell in response to danger signals [21; 22]. While an important part of the immune response, inflammasome activation has been implicated in the pathogenesis of a wide range of human diseases [23]. Through its receptor, VD appears to be able to inhibit inflammasome assembly and attenuate over-zealous inflammatory responses in animal models of disease [18; 20].  
This review will focus on the specific role VD may play in moderating inflammasome activity, in particular from the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, and examine the evidence for VD supplementation in conditions where the inflammasome is implicated.