title: A protective role for IL-13 receptor α 1 in bleomycin-induced pulmonary injury and repair.
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.
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, The Tel-Aviv University, Ramat Aviv, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Karo-Atar
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, The Tel-Aviv University, Ramat Aviv, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Bordowitz
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, The Tel-Aviv University, Ramat Aviv, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Wand
authors.affiliation: Bioinformatics Unit, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.affiliation: Comprehensive Pneumology Center, Ludwig Maximilians University, University Hospital Grosshadern, and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany.
authors.forename: I E
authors.initials: IE
authors.lastname: Fernandez
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, The Tel-Aviv University, Ramat Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Itan
authors.affiliation: Department of Math, Physics and Computer Science, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: R
authors.initials: R
authors.lastname: Frenkel
authors.affiliation: Division of Experimental Medicine, University of California, San Francisco, California, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Herbert
authors.affiliation: Division of Allergy, Immunology and Rheumatology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.|Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, USA.|Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: F D
authors.initials: FD
authors.lastname: Finkelman
authors.affiliation: Comprehensive Pneumology Center, Ludwig Maximilians University, University Hospital Grosshadern, and Helmholtz Zentrum München, Member of the German Center for Lung Research, Munich, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Eickelberg
authors.affiliation: Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, The Tel-Aviv University, Ramat Aviv, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Munitz
mesh_terms: D000328:Adult; D000818:Animals; D001761:Bleomycin; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology*; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D020381:Interleukin-17; D020033:Protein Isoforms; D019948:Receptors, Interleukin-4; D001761:Bleomycin; D015847:Interleukin-4