CTSD-deficiency in macrophages links impaired lysosomal function to immune-mediated pathology across different organs

Project Summary

In this project we 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 and subsequent immune-mediated pathology. 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. Furthermore, we aim to use the obtained results to unravel therapeutic interventions for immunopathologies caused by lysosomal insufficiency of TRM, for example by modulating overactivated inflammatory signaling cascades in TRM.