NALP3 IN IMMUNITY · In vivo analysis of NALP3, a protein implicated in three dominantly inherited syndromes, using knock-out and transgenic mice models
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-06-01 → 2007-05-31
- EU contribution
- €143,453
- Participants
- 1
- Scheme
- EIF
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Results in brief
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.
Data: CORDIS, © European Union
Project objective
The mechanisms involved in innate immune responses against pathogens are strikingly conserved during evolution. In plants, as well as in mammals, the innate immune system achieves its role of defence against pathogens through the use of specific pathogen r ecognition receptors, all containing a conserved LRR domain involved directly in pathogen-associated molecular pattern recognition. In mammals, transmembrane receptors associated with pathogen recognition are well described, but the existence of intracellu lar pathogen receptors is just emerging, with the recent description of a new family of human intracellular LRR domain containing proteins named CATERPILLER. These proteins are expected to play key roles in immune responses against pathogens, but to date, their roles are still poorly defined. Here, we propose to study one of these putative intracellular pathogen receptor, NALP3, which is implicated in three human dominantly-inherited inflammatory syndromes. We plan to 1) characterise the tissue specificity of Nalp3 expression in mice, and 2) use in vivo models consisting of Nalp3-deficient mice and NALP3 transgenic mice overexpressing the human wild-type or mutated proteins, to gain insight into 2.1) the role of Nalp3 protein in the mouse innate immunity, 2. 2) the mechanisms involved in intracellular pathogen recognition and 2.3) the role of the human NALP3 protein and its involvement in inherited inflammatory disorders.
Original text from CORDIS.
Participants
- UNIVERSITY OF LAUSANNE, DEPARTMENT OF BIOCHEMISTRY · EPALINGESCoordinatorCity levelSwitzerland
Links
Data: CORDIS, © European Union