Ctsd-deficiency in macrophages links lysosomal dysfunction to immune-mediated pathology across different organs (C05*)

• Subject Area: Immunology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256073931

The project (Kierdorf), will study the role of lysosomal insufficiency induced by Cathepsin D (Ctsd)-deficiency in tissue-resident macrophage (TRM) homeostasis to define how this results in overactivation of TRM (excessive antigen presentation, cytokine and chemokine release) and subsequent immune-mediated pathology in brain, liver and spleen. The project aims to further uncover how environmental factors such as endogenous microbiota but also infections modulate the immune-mediated pathologies triggered by overactivated Ctsd-deficient TRM. Finally, immunopathology caused by Ctsd-deficient TRM will be targeted by modulating overactivated inflammatory signaling cascades in TRM including NLRP3 inflammasome activation and increased MHC-II surface expression.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1160: Immune-mediated pathology as a consequence of impaired immune reactions (IMPATH)
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Head: Professorin Dr. Katrin Kierdorf