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Assessing the unified airway hypothesis in children via transcriptional profiling of the airway epithelium
- Source :
- The Journal of allergy and clinical immunology. 145(6)
- Publication Year :
- 2019
-
Abstract
- Background Emerging evidence suggests that disease vulnerability is expressed throughout the airways, the so-called unified airway hypothesis, but the evidence to support this is predominantly indirect. Objectives We sought to establish the transcriptomic profiles of the upper and lower airways and determine their level of similarity irrespective of airway symptoms (wheeze) and allergy. Methods We performed RNA sequencing on upper and lower airway epithelial cells from 63 children with or without wheeze and accompanying atopy, using differential gene expression and gene coexpression analyses to determine transcriptional similarity. Results We observed approximately 91% homology in the expressed genes between the 2 sites. When coexpressed genes were grouped into modules relating to biological functions, all were found to be conserved between the 2 regions, resulting in a consensus network containing 16 modules associated with ribosomal function, metabolism, gene expression, mitochondrial activity, and antiviral responses through IFN activity. Although symptom-associated gene expression changes were more prominent in the lower airway, they were reflected in nasal epithelium and included IL-1 receptor like 1, prostaglandin-endoperoxide synthase 1, CCL26, and periostin. Through network analysis we identified a cluster of coexpressed genes associated with atopic wheeze in the lower airway, which could equally distinguish atopic and nonatopic phenotypes in upper airway samples. Conclusions We show that the upper and lower airways are significantly conserved in their transcriptional composition, and that variations associated with disease are present in both nasal and tracheal epithelium. Findings from this study supporting a unified airway imply that clinical insight regarding the lower airway in health and disease can be gained from studying the nasal epithelium.
- Subjects :
- 0301 basic medicine
Male
Adolescent
Immunology
Respiratory System
IL1RL1
Respiratory Mucosa
Periostin
Biology
Transcriptome
03 medical and health sciences
0302 clinical medicine
Gene expression
Hypersensitivity
Immunology and Allergy
Humans
Child
Gene
Respiratory Sounds
Receptors, Interleukin-1 Type I
Chemokine CCL26
Epithelial Cells
respiratory system
030104 developmental biology
030228 respiratory system
Child, Preschool
Cyclooxygenase 1
Respiratory epithelium
Female
CCL26
Airway
Cell Adhesion Molecules
Subjects
Details
- ISSN :
- 10976825
- Volume :
- 145
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- The Journal of allergy and clinical immunology
- Accession number :
- edsair.doi.dedup.....bc58fd7c4b5e1358413a0f4e09fea284