Presentation Details
Investigating Inflammatory Modulation of Olfactory Sensory Neurons and Immune Cell Populations in the Main Olfactory Epithelium

Ryan E.Owens1, 2, 4, Varun Haran3, , Chinyi Chu4, , Julian P.Meeks3, , Regina K.Rowe3, .

1Department of Environmental Medicine, Rochester, NY, USA.2Toxicology Graduate Program, Rochester, NY, USA.3Department of Neuroscience, Rochester, NY, USA.4Department of Pediatrics, Rochester, NY, USA.5University of Rochester Medical Center, Rochester, NY, USA

Abstract


The nasal epithelium, a frontline defense against inhaled exposures, also contains the main olfactory epithelium (MOE), the site of olfaction. MOE dysfunction, resulting in hyposmia or anosmia, significantly impacts quality of life. The MOE’s diverse cell types include olfactory sensory neurons (OSNs), supporting, epithelial, and immune cells. Neuronal-immune communication in the MOE is relevant in diseases with olfactory dysfunction (e.g., allergic rhinitis or respiratory infections). OSNs must maintain olfactory function during inflammation, then subsequently repair during recovery. However, inhaled substances and odors may activate both OSNs and local immune cells. We hypothesized that resident immune cells and olfactory neurons are activated by olfactory stimuli and inflammatory mediators. Using single-cell RNA sequencing and flow cytometry, multiple subsets of OSNs, support, and immune cells were identified in the MOE. Using confocal microscopy, we found that in areas where OSNs and CD45+ resident immune cells were in close proximity, immune cells localized to both apical and basolateral regions. Ex vivo, we functionally assessed immunogenic and non-immunogenic stimuli on OSN and resident immune cell activation in mice expressing a genetically encoded Ca2+ indicator, GCaMP6s, in either OSNs (Omp-Cre x Ai96) or immune cells (Cx3cr1-Cre x Ai96) isolating MOEs en bloc and exposing to stimuli. Using volumetric objective-coupled planar illumination (OCPI) microscopy we identify and measure Ca2+ activity during stimulation resulting in mixed sensitivities across cells. These findings provide preliminary evidence of interactions between resident immune cells and olfactory neurons, with future studies using this experimental system to further evaluate the influence of mucosal inflammation.    

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