Homeostatic mechanisms supporting the maintenance of tissue-resident macrophages
Principal Investigator
Scientific interest within the context of the graduate college:
Active maintenance of tissue health requires maintenance of tissue-resident macrophages that perform homeostatic functions. Loss of tissue-resident macrophages reduces the ability of tissues to maintain homeostasis or to return to homeostasis after inflammation. We propose that exploring the mechanisms that maintain tissue-resident macrophages will allow us to identify molecular targets that promote tissue health and to achieve deeper remission after treatment of chronic inflammatory diseases.
Project description:
Tissue-resident macrophages play an active role in maintaining tissue homeostasis. The clearance of apoptotic cells and other tissue debris, the immediate immune response to pathogens, and metabolic regulation are all functions of tissue resident macrophages that are essential for tissue health. Failure to maintain the tissue-resident macrophage population during aging, or loss of tissue-resident macrophages in chronic inflammation results in loss of tissue function. Despite their importance, the mechanisms that actively maintain tissue-resident macrophages in healthy tissues are largely unknown. The current project is based on extensive preliminary data from our lab that have uncovered a novel pathway required for the maintenance of tissue-resident macrophages.
The project will explore the mechanisms that maintain tissue-resident macrophages across different organs, including macrophage populations of different origins, and in response to various acute inflammatory stimuli, such as TNF and type I interferons. The project will further compare the mechanisms that regulate tissue-resident macrophage populations in homeostasis versus in chronic inflammatory diseases. Overall, this line of work aims to uncover essential pathways that promote tissue-resident macrophage maintenance and thus tissue health, paving the way for a deeper remission following treatment of chronic inflammatory diseases.