Defining the molecular and anatomical basis of the blood-olfactory barrier (BOB)

点击翻译按钮获取中文摘要

The upper respiratory tract is lined by two distinct types of epithelium. Respiratory epithelium humidifies and modulates incoming air temperature as it passes toward the lungs. Olfactory epithelium on the other hand is specialized for chemosensation and supports detection of airborne odorants by olfactory sensory neurons (OSNs). We have recently described that blood vessels within the olfactory mucosa form a “blood -olfactory barrier” (BOB) that prevents high molecular weight blood borne proteins from accessing the olfactory tissues. This BOB effectively isolates olfactory tissues from blood borne molecules in much the same way that the blood brain barrier and the blood retinal barrier function in the brain and eye. In our studies we found that antibodies (~150kD) against viral pathogens cannot exit the blood to prevent infections within the olfactory epithelium. The existence of the BOB may help reconcile years of seemingly contradictory upper airway immunity data, and also helps explain why pathogens such as SARS-CoV-2 that infect the olfactory epithelium cause “breakthrough infections” when blood antibody titers are high. We know very little about the basic cellular and molecular building blocks of this newly defined vascular barrier. This proposal will establish the limits of BOB homeostatic permeability and several foundational insights about the BOB, including: BOB functionality from developmental stages until late adulthood, determine the cellular and junctional makeup that generates the BOB, define the functional permeability limits during health and inflammation, and finally determine the role of olfactory neurons in orchestrating olfactory barrier identity.