Oncostatin-M Is Produced by Human Eosinophils and Associates with Asthma Severity
Eosinophils are a hallmark of asthma, and oncostatin-M (OSM) is a protein that activates fibroblasts, epithelial cells, and smooth muscle cells. The production of OSM by mature human eosinophils has not been reported. To demonstrate the production and release of OSM by eosinophils, and to analyze the production of OSM in vivo following a segmental bronchoprovocation with an allergen (SBPAg) in humans. Blood eosinophils were separated and activated in vitro. Expression of OSM was determined by RNA-sequencing (RNAseq) and the release of OSM protein was quantified by ELISA. In addition, OSM protein in bronchoalveolar lavage (BAL) and OSM expression in bronchial epithelial (BE) brushing samples after SBP-Ag were quantified by O-link Proteomics technology and RNA-seq, respectively. Eosinophils released OSM protein in vitro. After SBPAg, the amount of BAL OSM correlated with the number of BAL eosinophils, reduced lung function, and proteins involved in inflammation and tissue remodeling. BE brushing samples revealed associations between OSM expression level and transcripts related to inflammatory response, antigen processing and presentation, and granulocyte activation. Lastly, compared to blood eosinophils from healthy individuals and patients with CRSwNP, blood eosinophils from severe asthma expressed enhanced levels of OSM mRNA, which was associated with markers of loss of asthma control. OSM is produced by eosinophils. The associations of OSM with inflammation, tissue remodeling, poorer lung function, uncontrolled asthma, and airway eosinophilia reveal that OSM may be an important target in eosinophilic severe asthma.