Comprehensive mapping of the neuro-immune interface at pancreatic islets during type 1 diabetes

Diabetes mellitus type 1 (T1D) affects around 425 million people worldwide and has an increasing prevalence.

During T1D progression, beta cells in the pancreatic islets and nerve network are destroyed in an autoimmune process resulting in insulin dependence, lifelong treatment and severe long-term complications such as cardiovascular diseases, nerve damages and lower-limbamputations. Insights into how nervous input can influence behaviors of immune cells are rapidly increasing.

Thereby a key question arising in T1D research is how neurotransmitters are regulated in the pancreatic islets in health and disease.

Recent data from mouse models suggest a major influence from sympathetic signaling via neurotransmitters in regulating immune cells during the autoimmune disease progression.

I  hypothesise that the pancreatic nerve network and/or its  regulation in pre-T1D is altered which leads to a shift in neurotransmitter levels and activity, in turn leading to dysregulation of the immune environment and rendering the beta cells susceptible to an autoimmune attack.

Therefore, my goal is to elucidate the regulation of intra-islet neurotransmitters and macrophages and its effect on T1D onset via1) Mapping of neurotransmitter levels and nerve activity in the pancreas during T1D onset, and2) Determine macrophage dynamics to secreted neurotransmitter in T1D onset in mice and  human.To address this, I will use state-of-the-art imaging models, spatial mass spectrometry, human PET imaging, murine 3D co-cultures and specialized high-throughput human coculture system.

Altogether, this data from human and mouse pancreata will help to understand the influence of neurotransmitter levels on macrophage infiltration and beta-cell damage in T1D.

Knowing how neurotransmitter levels change in different contexts and disease progression provides the  opportunity to identify new biomarkers or interfere in specific neurotransmitter levels for future treatment of T1D patients.