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Publication : Oncostatin M expression induced by bacterial triggers drives airway inflammatory and mucus secretion in severe asthma.

First Author  Headland SE Year  2022
Journal  Sci Transl Med Volume  14
Issue  627 Pages  eabf8188
PubMed ID  35020406 Mgi Jnum  J:334058
Mgi Id  MGI:7311841 Doi  10.1126/scitranslmed.abf8188
Citation  Headland SE, et al. (2022) Oncostatin M expression induced by bacterial triggers drives airway inflammatory and mucus secretion in severe asthma. Sci Transl Med 14(627):eabf8188
abstractText  Exacerbations of symptoms represent an unmet need for people with asthma. Bacterial dysbiosis and opportunistic bacterial infections have been observed in, and may contribute to, more severe asthma. However, the molecular mechanisms driving these exacerbations remain unclear. We show here that bacterial lipopolysaccharide (LPS) induces oncostatin M (OSM) and that airway biopsies from patients with severe asthma present with an OSM-driven transcriptional profile. This profile correlates with activation of inflammatory and mucus-producing pathways. Using primary human lung tissue or human epithelial and mesenchymal cells, we demonstrate that OSM is necessary and sufficient to drive pathophysiological features observed in severe asthma after exposure to LPS or Klebsiella pneumoniae. These findings were further supported through blockade of OSM with an OSM-specific antibody. Single-cell RNA sequencing from human lung biopsies identified macrophages as a source of OSM. Additional studies using Osm-deficient murine macrophages demonstrated that macrophage-derived OSM translates LPS signals into asthma-associated pathologies. Together, these data provide rationale for inhibiting OSM to prevent bacterial-associated progression and exacerbation of severe asthma.
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