Neuroimmune interactions in the pancreas in health and disease- Identifying the components of nerve-macrophage association 2911

Abstract Description Type 1 Diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β-cells, resulting in reduced insulin secretion and hyperglycaemia. While the exact cause remains unknown, studies in mouse models indicate that sympathetic denervation and macrophage depletion can halt T1D progression, suggesting a critical role for neuroimmune communication in the disease’s development. Nerve-associated macrophages (NAMs), which express high levels of CX3CR1 similar to microglia, have been identified across various organs, highlighting the importance of CX3CR1 in nerve-macrophage interactions. In pancreatic islets, we observed reduced innervation and diminished nerve-macrophage association in CX3CR1 knock-out mice. Similar findings in the kidneys and lungs suggest that CX3CR1’s role extends beyond islet tissue. Additionally, inducing diabetes in animals with CX3CR1 knocked out resulted in a reduction in T1D progression, underscoring the potential impact of this receptor on disease development. Utilizing NAM signature in single cell sequencing analysis of macrophages isolated from non-obese diabetic (NOD) mice, we confirmed the presence of NAMs in islets. Next, we will use a in house developed 3D co-culture model to study dynamic nerve-islet-macrophage interactions, and live pancreatic tissue slices to examine neurotransmitter effects on macrophages. Studying human pancreatic slices aims to reveal new neuro-immune pathways in T1D, with potential treatment targets. Topic Categories Neuroimmunology (NEUR)