A protective role for IL-13 receptor α 1 in bleomycin-induced pulmonary injury and repair

Karo-Atar, D.; Bordowitz, A.; Wand, O.; Pasmanik-Chor, M.; Fernandez, I. E.; Itan, M.; Frenkel, R.; Herbert, D. R.; Finkelman, F. D.; Eickelberg, O. und Munitz, A. (2016): A protective role for IL-13 receptor α 1 in bleomycin-induced pulmonary injury and repair. In: Mucosal Immunology, Bd. 9, Nr. 1: S. 240-253

Abstract

Molecular mechanisms that regulate lung repair vs. progressive scarring in pulmonary fibrosis remain elusive. Interleukin (IL)-4 and IL-13 are pro-fibrotic cytokines that share common receptor chains including IL-13 receptor (R) alpha 1 and are key pharmacological targets in fibrotic diseases. However, the roles of IL-13R alpha 1 in mediating lung injury/repair are unclear. We report dysregulated levels of IL-13 receptors in the lungs of bleomycin-treated mice and to some extent in idiopathic pulmonary fibrosis patients. Transcriptional profiling demonstrated an epithelial cell-associated gene signature that was homeostatically dependent on IL-13R alpha 1 expression. IL-13R alpha 1 regulated a striking array of genes in the lung following bleomycin administration and Il13ra1 deficiency resulted in exacerbated bleomycin-induced disease. Increased pathology in bleomycin-treated Il13ra1(-/-) mice was due to IL-13R alpha 1 expression in structural and hematopoietic cells but not due to increased responsiveness to IL-17, IL-4, IL-13, increased IL-13R alpha 2 or type 1 IL-4R signaling. These data highlight underappreciated protective roles for IL-13R alpha 1 in lung injury and homeostasis.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1933-0219
• Sprache: Englisch