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.
Subject(s)
Idiopathic Pulmonary Fibrosis/immunology , Interleukin-13 Receptor alpha1 Subunit/immunology , Interleukin-13/immunology , Lung Injury/immunology , Adult , Animals , Bleomycin , Case-Control Studies , Female , Gene Expression Regulation , Homeostasis/immunology , Humans , Idiopathic Pulmonary Fibrosis/chemically induced , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/pathology , Interleukin-13/genetics , Interleukin-13 Receptor alpha1 Subunit/deficiency , Interleukin-13 Receptor alpha1 Subunit/genetics , Interleukin-17/genetics , Interleukin-17/immunology , Interleukin-4/genetics , Interleukin-4/immunology , Lung/immunology , Lung/pathology , Lung Injury/chemically induced , Lung Injury/genetics , Lung Injury/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Middle Aged , Protein Isoforms/genetics , Protein Isoforms/immunology , Receptors, Interleukin-4/genetics , Receptors, Interleukin-4/immunology , Signal Transduction , Transcription, GeneticABSTRACT
A case of Leber's amaurosis congenita is presented. The patient was bilaterally and congenitally blind. She had nonrecordable ERG responses and a striking fundus appearance with multiple irregularly shaped yellowish white flecks deep in the retina, peripheraly distributed over an area extending from behind the equator to the ora serrata. No flecks were present in narrow bands on both sides of the retinal vessels and in the whole nasal portion of the fundus. Fine powdery granules of pigment were diffusely spread in the areas that were devoid of flecks. The macula and the optic disc showed no gross abnormality. Although this fundus appearance resembles that of the flecked retina syndrome and Oguchi's disease, retinal function in this case is more profoundly affected than in either of the two.
