Autophagy mechanisms in intercellular sensing of tissue homeostasis by the immune system

 

Disturbance of tissue homeostasis is sensed by the immune system in order to initiate adaptive measures. Non-canonical autophagy encompasses major mechanisms of cellular homeostasis, but how such mechanisms and their failure are sensed by the immune system at the tissue level is poorly understood. In this project, we explore the homeostatic response of the immune system to selected autophagy pathways in neighboring cells. Specifically, we focus on the regulation of MHC-I-like molecule expression and localization, and the role of secretory autophagy, which orchestrates cellular secretion of a variety of cargo via extracellular vesicles (EVs) to the biology of recipient cells. We aim to investigate how secretory autophagy and the impact of autophagy on MHC-I-like molecules shape the immune response under both intact and disturbed homeostasis. To that end, we employ a number of state-of-the art techniques including genetic screens, high-parameter multispectral imaging, automated high content microscopy, and various Omics techniques in murine and human models. Our studies will reveal how the autophagy machinery shapes immune-dependent tissue homeostasis.

 

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