Final Activity Report Summary - NALP3 IN IMMUNITY (In vivo analysis of NALP3, a protein implicated in three dominantly inherited syndromes, using knock-out and transgenic mice models)
Inflammasomes are molecular platforms that lead to the activation of inflammatory caspases and to the secretion of IL-1beta, a key pyrogenic cytokine. Inflammasomes are activated by danger signals like uric acid crystals as well as by microbial products. Dysregulation of IL-1beta is associated with many disorders and the characterisation of inflammasomes by the group of professor Tschopp, allowed the treatment of some of these disorders by the use of an IL-1beta antagonist. As pyrin was a strong candidate for regulating inflammasome activity, one of my projects was the evaluation of the role of pyrin in the context of inflammasomes regulation and IL-1beta secretion. We could demonstrate that pyrin is an inhibitor of inflammasomes through its binding to both caspase-1 and pro-IL-1beta. We also found that potassium variations within the cell are involved in the activation of inflammasomes, indicating that ionic variations make the link between different stimuli and inflammasomes, through as yet unclear mechanisms.