Pyrin Inflammasome Activation Triggers an IL-18-Driven IFNγ Response in Mevalonate Kinase Deficiency - PubMed
7 hours ago
- #Mevalonate Kinase Deficiency
- #Inflammasome
- #Autoinflammation
- Mevalonate kinase deficiency (MKD) is a rare autoinflammatory disorder caused by MVK gene mutations, leading to pyrin inflammasome activation.
- A THP1 monocyte cell line with MVK I268T mutations was created using CRISPR/Cas9 to model MKD and study inflammatory pathways.
- MVK-deficient cells showed impaired isoprenoid biosynthesis and increased IL-1β and IL-18 secretion upon pyrin inflammasome activation.
- MKD patient PBMCs and plasma exhibited elevated IL-18 and IFNγ levels, indicating an IL-18/IFNγ inflammatory axis.
- The study suggests targeting the pyrin-inflammasome-driven IL-18/IFNγ pathway as a potential therapeutic strategy for MKD.