Deciphering pulmonary neuroimmune circuits in health and disease

Interactions between neuronal and immune cells have been reported to regulate organ physiology and to contribute to several disorders, including inflammation and infection. These findings are provoking a fundamental paradigm shift in our understanding of tissue physiology, neuroimmune interactions and their potential therapeutic value. Nevertheless, the underlying mechanisms of this crosstalk are still poorly understood and further progress in this field has been hindered by a lack of approaches to quantify neuroimmune interactions in vivo.

Here, we propose the use of innovative intercellular labelling methods to characterize, quantify and manipulate neuroimmune interactions with single cell resolution and unprecedented mechanistic detail. To this end, we have developed viral- and genetic-based techniques which we term “Kindle Intercellular Signals and Synapses” KISS to interrogate neuroimmune interaction partners in vivo. Our analysis will focus on the respiratory tract, determining how the neuronal and immune cell crosstalk is regulated in the context of health and disease.

By capitalizing on recent developments in immunology and neuroscience, this project will result in a high-resolution map of the connectivity, molecular identity and functional profile of the neuroimmune interface. These comprehensive data on broad cell-cell interactions will unlock an entire layer of knowledge of how the neuroimmune “interactome” unfolds in health and disease. Finally, the comprehensive understanding of peripheral neuroimmune circuits will pave the way to the discovery of innovative therapeutic targets in the broad context of infectious, neurologic, metabolic and oncologic conditions.