Genome-Wide Gene Expression Analysis Reveals Unique Genes Signatures of Epithelial Reorganization in Primary Airway Epithelium Induced by Type-I, -II and -III Interferons.
Anna ErbUlrich M ZisslerMadlen OelsnerAdam M ChakerCarsten B Schmidt-WeberConstanze A JakwerthPublished in: Biosensors (2022)
Biosensors such as toll-like receptors (TLR) induce the expression of interferons (IFNs) after viral infection that are critical to the first step in cell-intrinsic host defense mechanisms. Their differential influence on epithelial integrity genes, however, remains elusive. A genome-wide gene expression biosensor chip for gene expression sensing was used to examine the effects of type-I, -II, and -III IFN stimulation on the epithelial expression profiles of primary organotypic 3D air-liquid interface airway cultures. All types of IFNs induced similar interferon-stimulated genes (ISGs): OAS1, OAS2, and IFIT2. However, they differentially induced transcription factors, epithelial modulators, and pro-inflammatory genes. Type-I IFN-induced genes were associated with cell-cell adhesion and tight junctions, while type-III IFNs promoted genes important for transepithelial transport. In contrast, type-II IFN stimulated proliferation-triggering genes associated and enhanced pro-inflammatory mediator secretion. In conclusion, with our microarray system, we provide evidence that the three IFN types exceed their antiviral ISG-response by inducing distinct remodeling processes, thereby likely strengthening the epithelial airway barrier by enhancing cross-cell-integrity (I), transepithelial transport (III) and finally reconstruction through proliferation (II).
Keyphrases
- genome wide
- dna methylation
- gene expression
- bioinformatics analysis
- genome wide identification
- immune response
- dendritic cells
- single cell
- high glucose
- copy number
- transcription factor
- cell adhesion
- cell therapy
- drug induced
- diabetic rats
- magnetic resonance
- endothelial cells
- computed tomography
- type iii
- stem cells
- genome wide analysis
- inflammatory response
- quantum dots
- poor prognosis
- high throughput
- bone marrow
- circulating tumor cells
- nuclear factor