Cell Type-Specific Role of the Inflammasome-like Receptor NLRP10 in Cardiac Lesions (B10 (P10))

• Subject Area: Cardiology, Angiology ; Immunology ; Cell Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422681845

Our prior work identified a cardioprotective role for NLRP10 in heart lesions. The mechanistic basis for this, i.e. the signals involved and the downstream pathways engaged, remains unknown. To elucidate this, we will use specific deletion and rescue of NLRP10 in cardiomyocytes in our transverse aortic constriction (TAC) lesion model. Cellular stress signals, triggering NLRP10 and its cellular (re)localization, will be studied in primary murine cardiomyocytes cultures using synthetic reporter systems we have developed. Both unbiased and hypothesis-driven approaches, involving sequencing of nuclear RNA and ATAC-seq, as well as studies on mice deficient in common components of NLR signaling pathways, will serve to reveal downstream pathways engaged by NLRP10 upon TAC-induced remodeling. The effect of NLRP10-deficiency in cardiomyocytes on other cardiac cell populations will be mapped using flow cytometry and RNA-seq. Finally, overexpression by virus-mediated gene delivery will serve to elucidate the therapeutic potential of NLRP10, which we regard as a potential translational target.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1425: Heterocellular Nature of Cardiac Lesions: Identities, Interactions, Implications
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Head: Professor Dr. Olaf Groß