Interferon-α exerts proinflammatory properties in experimental radiation-induced esophagitis: Possible involvement of plasmacytoid dendritic cells

Aims: Radiation-induced esophagitis, experienced during radiation therapy for lung cancer and head and neck cancer, is a major dose-limiting side effect of the treatment. This study aimed to elucidate the role of interferon-alpha (IFN-alpha) in radiation-induced esophagitis. Main methods: C57BL/6 mice were exposed to 10 and 25 Gy of single thoracic irradiation. Esophageal mucosal damage and inflammatory reactions were assessed for 5 days after irradiation. Key findings: Irradiation induced esophagitis, characterized by reduction in the thickness of epithelial layer, upregulation of proinflammatory cytokines and chemokines, infiltration of inflammatory cells into the esophageal mucosa, and apoptosis of epithelial cells. Irradiation upregulated the level of gene expression for IFN-alpha in the esophageal tissue, and the neutralizing antibody against IFN-alpha ameliorated radiation-induced esophageal mucosal damage, while administration of IFN-alpha receptor agonist (RO8191) had an inverse effect. Depletion of plasmacytoid dendritic cells (pDCs) by anti-CD317 antibody or pharmacological inactivation with bortezomib suppressed radiation-induced mucosal inflammation and damage, accompanied by decrease in IFN-alpha expression level. Significance: These findings suggest that IFN-alpha and pDCs exert proinflammatory properties in the pathophysiology of radiation-induced esophagitis.