DNeurImmKisses has been developing and implementing complementary approaches to interrogate neuroimmune circuits connecting the nervous system to immune cells in different organs of the body. Notably, we have been focusing our work on lung, intestine, pancreas and renal neuroimmune circuit architecture.
We investigated how neuroimmune interactions orchestrate pancreatic endocrine function. We discovered that when blood sugar levels are suboptimal, the adrenergic nervous system instructs intestinal immune cells to migrate to the pancreas, where they trigger the endocrine activity or this organ, thus reestablishing optimal sugar concentrations. These results revealed a neuroimmune inter-organ communication route that promotes pancreatic function and regulation of blood sugar levels.
In parallel we interrogated how intestinal neurons calibrate local immunity to infection. We discovered that intestinal neurons interact with local epithelial cells, forming neuroepithelial units that regulate immune responses against infection. This work identified a multi-tissue axis whereby neuroepithelial interactions distinctively set gut immunity programs (Pirzgaslka et al. Nature Immunol. 2025; Jakob et al. Nature Immunol. 2025).
During the first two years, we mainly focused on building and optimising tools that allow us to track and measure communication between nerves and immune cells directly in living tissues. We implemented viral tracing strategies and created new mouse models in which specific nerve cells can label the immune cells they contact, providing a “history” of recent neuro‑immune interactions. In parallel, we optimised an approach that uses an enzyme and a small tagged peptide to permanently mark immune cells that have recently touched defined groups of neurons or glial cells. We also established a conditional model to switch off a key receptor for the neuropeptide VIP in selected cell types, which will allow us to test how this signal contributes to lung inflammation and repair. Together, these tools now put the project in a strong position to dissect how nerves attract ILC2 into particular lung niches and how this shapes allergy, infection and tissue regeneration.
