Basophils activate oncostatin M receptor-expressing vagal sensory neurons.

Abstract

BACKGROUND: Vagal sensory neurons (VSNs) relay signals from internal organs to the brainstem via the vagus nerve. Published transcriptomic data sets suggest that VSNs express Mas-related G protein-coupled receptor family member D and oncostatin M (OSM) receptor, markers also found in dorsal root ganglia-resident pruriceptor neurons. However, the cellular source of OSM and its potential interactions with VSNs remain unknown. OBJECTIVE: We sought to validate the expression of pruritogen receptors on VSNs, identify basophils as a source of OSM, and determine how OSM modulates VSN activity. METHODS: Pruritogen receptor expression on VSNs was validated by immunofluorescence staining, and VSN responses to pruritogens were assessed using in vitro and in vivo calcium imaging. Mouse models of allergic airway inflammation, fluorescence-activated cell sorting, quantitative PCR, and ELISA were used to evaluate OSM expression and production by lung basophils. RESULTS: Immunofluorescence and quantitative PCR confirmed that airway-innervating VSNs express OSM receptor and that lung basophils are enriched for Osm transcripts. Lung-resident basophils produced OSM following FcεRIα engagement, with production further enhanced after sensitization to house dust mite (Dermatophagoides pteronyssinus) or the fungal allergen Alternaria alternata. In vitro and in vivo calcium imaging revealed that OSM sensitizes multiple populations of VSNs. CONCLUSIONS: These findings identify a novel mechanism of communication between basophils and VSNs during type I hypersensitivity reactions, such as those occurring in allergic asthma.