Pancreatic macrophages: from ontogeny to phenotype and function

• Main Author: Ma, Ziyuan
• Other Authors: Ruedl Christiane
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2024
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/172964; https://doi.org/10.21979/N9/2YJP6X
• Institution: Nanyang Technological University

Tissue resident macrophages found throughout the body are highly heterogeneous with different origins, turnover kinetics and tissue specific functions. My project identifies four distinct resident macrophage subsets in the murine pancreas based on the expression of cell markers F4/80, MHCII, CD11c and Tim-4. Their numbers and relative abundance shift during aging, while the pancreas immune landscape remains relatively stable under obese and diabetic conditions. Ontogeny experiments reveal that pancreas resident macrophages originate from definitive hematopoiesis. Exocrine Tim4+ macrophages are long-lived and self-maintain with minimal monocyte replenishment, while Tim4- macrophages found in both the exocrine and endocrine are steadily replenished by monocytes. Depletion of pancreas resident macrophages induces an inflammatory response in the exocrine under diabetic conditions, while their absence from the endocrine improves diabetic symptoms. My results offer new insights into pancreas macrophage characteristics and may provide the basis for the development of alternative diabetes treatment.