BASOPHILS ACTIVATE PRURICEPTOR-LIKE VAGAL SENSORY NEURONS

ABSTRACT Vagal sensory neurons convey sensations from internal organs along the vagus nerve to the brainstem. Pruriceptors are a subtype of neurons that transmit itch and induce pruritus. Despite extensive research on the molecular mechanisms of itch, studies focusing on pruriceptors in the vagal ganglia still need to be explored. In this study, we characterized vagal pruriceptor neurons by their responsiveness to pruritogens such as lysophosphatidic acid, β -alanine, chloroquine, and the cytokine oncostatin M. We discovered that lung-resident basophils produce oncostatin M and that its release can be induced by engagement of Fc ε RI α . Oncostatin M then sensitizes multiple populations of vagal sensory neurons, including Tac1 + and MrgprA3 + neurons in the jugular ganglia. Finally, we observed an increase in oncostatin M release in mice sensitized to the house dust mite Dermatophagoides pteronyssinus or to the fungal allergen Alternaria alternata , highlighting a novel mechanism through which basophils and vagal sensory neurons may communicate during type I hypersensitivity diseases such as allergic asthma.