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Mucosal Immunol. 2016 Jan;9(1):240-53. doi: 10.1038/mi.2015.56. Epub 2015 Jul 8.

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

Author information

1
Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, The Tel-Aviv University, Ramat Aviv, Israel.
2
Bioinformatics Unit, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
3
Comprehensive Pneumology Center, Ludwig Maximilians University, University Hospital Grosshadern, and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany.
4
Department of Math, Physics and Computer Science, University of Cincinnati, Cincinnati, Ohio, USA.
5
Division of Experimental Medicine, University of California, San Francisco, California, USA.
6
Division of Allergy, Immunology and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
7
Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, USA.
8
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

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) α1 and are key pharmacological targets in fibrotic diseases. However, the roles of IL-13Rα1 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-13Rα1 expression. IL-13Rα1 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-13Rα1 expression in structural and hematopoietic cells but not due to increased responsiveness to IL-17, IL-4, IL-13, increased IL-13Rα2 or type 1 IL-4R signaling. These data highlight underappreciated protective roles for IL-13Rα1 in lung injury and homeostasis.

PMID:
26153764
PMCID:
PMC4703942
DOI:
10.1038/mi.2015.56
[Indexed for MEDLINE]
Free PMC Article

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