Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation

Author:

Wright Paulette L.1,Yu Jun1,Di Y.P. Peter2,Homer Robert J.3,Chupp Geoffrey1,Elias Jack A.1,Cohn Lauren1,Sessa William C.1

Affiliation:

1. Vascular Biology and Therapeutics Program, Departments of Pharmacology and Medicine, and Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510

2. Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219

3. Department of Pathology, Yale School of Medicine and Pathology and Laboratory Medicine Service, VA CT HealthCare System, West Haven, CT 06516

Abstract

Nogo-B is a member of the reticulon family of proteins (RTN-4B) that is highly expressed in lung tissue; however, its function remains unknown. We show that mice with Th2-driven lung inflammation results in a loss of Nogo expression in airway epithelium and smooth muscle compared with nonallergic mice, a finding which is replicated in severe human asthma. Mice lacking Nogo-A/B (Nogo-KO) display an exaggerated asthma-like phenotype, and epithelial reconstitution of Nogo-B in transgenic mice blunts Th2-mediated lung inflammation. Microarray analysis of lungs from Nogo-KO mice reveals a marked reduction in palate lung and nasal clone (PLUNC) gene expression, and the levels of PLUNC are enhanced in epithelial Nogo-B transgenic mice. Finally, transgenic expression of PLUNC into Nogo-KO mice rescues the enhanced asthmatic-like responsiveness in these KO mice. These data identify Nogo-B as a novel protective gene expressed in lung epithelia, and its expression regulates the levels of the antibacterial antiinflammatory protein PLUNC.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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