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Abstract
Vitamin D (VD) is a steroid hormone classically known for its key role in maintaining calcium homeostasis in the body. VD also has important immunomodulatory functions. This review explores evidence for a role of VD in attenuating the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Dysregulated and inappropriate NLRP3 inflammasome activation occurs in a range of human diseases, including autoinflammatory disorders, metabolic disorders, and infections. VD appears to mediate its effects by binding of the VD receptor (VDR) to the sensor protein NLRP3, inhibiting deubiquitination and downstream inflammasome assembly. Some early clinical evidence suggests improved outcomes in inflammasome-mediated disorders when VD-deficient patients are treated with supplementation therapy.