Deregulation of inflammasomes in autoinflammatory diseases
Inflammasomopathies can be classified in two groups: monogenic inflammasomopathies and complex inflammasomopathies.
Monogenic inflammasomopathies are due to mutations in inflammasome genes. Our main focus is on Familial Mediterraean Fever (FMF), an autoinflammatory disease associated with mutation in the MEFV gene encoding Pyrin, an inflammasome sensor.
We discovered that FMF-associated MEFV mutations decrease the threshold of activation of the pyrin inflammasome providing a first clue of why FMF patients suffer from recurrent episodes of inflammation. Full story here!
We then looked into the mechanistics of pyrin inflammasome in healthy donors and FMF patients to uncover the deregulation mechanisms. We discovered that the pyrin inflammasome is controlled by two mechanisms, one of it deficient in FMF patients. The full article by Flora Magnotti and her colleagues!
This work also highlighted that there is still a lot to learn on the pyrin inflammasome and its regulation both at steady state and during inflammation.
Studying rare monogenic diseases is important for patients suffering from these diseases but is also important to learn about complex inflammasomopathies. We are thus using our inflammasome expertise to investigate the deregulation of inflammation in several complex autoinflammatory diseases, including Still's disease. This work is largely based on immunophenotyping of primary human cells and is supported by European Union’s Horizon 2020 research and innovation programme. See ImmunAID project!