Sensing Neuro-immune Activation in the Lung microenvironment

ended

The immune system is indispensable for our defense against infections, and plays an essential role in homeostasis, where compartmentalization and specialization are key aspects of every immune cell. Microenvironmental cues (e.g. stromal cell-derived signals) are integrated by the cell networks forming the immune system to maintain immune tolerance or promote immunity against an antigen. Recent findings suggest that neurons also contribute to curb the immune response; they produce neuropeptides that act directly on immune cells such as dendritic cells and neutrophils. However, our understanding of neuroimmune interactions is superficial: we ignore whether specialized cell subsets are responsible for integrating neural cues, we lack precision when studying these connections, and it is unknown whether neuroimmune exchanges are relevant in different tissues and immune reactions, as with the case of lung immune responses related to allergy and chronic obstructive disorders. Asthma has been shown to present a neurological component not yet entirely linked to the immune system. To gain insight into neuroimmune modulation, SIGNAL aims to elucidate the presence and function of neuro-sentinel innate lymphoid cells (nsILC) in the lung: ILC dedicated to detect and translate neuro-derived signals. ILC are tissue resident immune cells which are pivotal coordinators of immune homeostasis, bridging the innate and the adaptive immune system. Using a multidisciplinary approach by combining the selectiveness of optogenetics and chemogenetics with the unbiased power of detection of single cell genomics, and the comprehensiveness of mouse in vivo models, I have setup myself to discover and define nsILC in the context of type-2 responses in the lung. My work will develop our understanding of neuroimmune interactions, and their influence in allergy and asthma, potentially discovering pathways which will provide the context for new approaches in treating this type of disorders.