Deciphering the functional role of commensal-induced T-DC clustering along sensory nerves in the lung

Abstract The airway mucosa is a primary site of the immune response to inhaled antigens. However, how homeostasis maintained in this organ during continuous exposure airborne particles and microbial antigens not known. Previous studies have shown that spatial organization components relationship each other non-hematopoietic tissues critical their proper function, as communication with commensal microbes. To interrogate such relationships lung, especially possible connections between cells densely innervated pulmonary airway, 3D information required. current methods for imaging optically cleared tissue do provide marker depth afforded by high-content 2D imaging. overcome constraint, we combined fast hydrophilic clearing technique, Ce3D, recently developed IBEX created Ce3D-IBEX. date, up 20 markers been visualized single sample. Using Ce3D-IBEX, identified previously uncharacterized clustering T dendritic proximity sensory nerves naïve mice. Agonistic denervation resiniferatoxin reduced number clusters, cluster formation was disrupted germ-free mice well OT-I OT-II TCR-Tg These findings indicate requires nerve-derived signals TCR-mediated recognition bacterial Future will be aimed at elucidating functional role clusters disease conditions determining molecular basis neuro-immune regulates activity. All were done approval from ICUC NIH/NIAID. This work supported Intramural Research Program NIAID, NIH.