Regulation of the Nlrp1a inflammasome in cutaneous and systemic autoinflammation

The human inflammasome sensor NLRP1 plays an important role in UVB irradiation-induced skin inflammation and activating germline mutations in NLRP1 were recently shown to cause rare, but severe systemic autoinflammatory diseases that affect the skin and lung epithelium. The proposed studies will clarify how NLRP1 promotes pathological inflammation by addressing the transcriptional and post-translational mechanisms that regulate expression and activation of the orthologous murine Nlrp1a inflammasome in pathophysiologically relevant cell types. Moreover, the in vivo mechanisms of Nlrp1a-driven autoinflammatory disease will be studied in innovative mouse models of systemic and cutaneous inflammation.