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Influenza virus-induced type I interferons disrupt alveolar epithelial repair and tight junction integrity in the developing lung

ABSTRACT: Influenza virus-induced type I interferons disrupt alveolar epithelial repair and tight junction integrity in the developing lung

PROVIDER: PRJNA1211121 | ENA |

REPOSITORIES: ENA

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Influenza virus-induced type I interferons disrupt alveolar epithelial repair and tight junction integrity in the developing lung

Project description:Type I interferons (IFN-I) are key innate immune mediators which control viral infection in adults. Recently, using a neonatal murine model of influenza A infection (IAV), we demonstrated that IAV-infected murine neonates lacking a functional IFN-I receptor (IFNAR-/-) have significantly improved survival and reduced lung pathology relative to wild-type (WT) neonates. However, the opposite is observed in adults, with IAV-infected IFNAR-/- adults exhibiting enhanced morbidity relative to WT adults, indicating an age-specific IFN-I toxicity in neonates. Therefore, we hypothesized that IAV-induced IFN-I signaling in primary neonatal type II alveolar epithelial cells (TIIECs), the main cell type of IAV infection and initiator of host response in the lung, contributed to age-specific viral pathogenesis. To investigate the role of IFN-I signaling in TIIECs, we performed RNA-Seq on purified TIIECs in a multifactorial design, comparing 1. IFNAR-/- and WT genotypes, 2. neonatal and adult ages, 3. IAV-infected and uninfected, 4. over a three-day time course.Analysis of purified TIIECs revealed age, not infection status, as the primary driver of transcriptional differences in TIIECs. Subsequent pathway analysis demonstrated IAV-infected IFNAR-/- neonates significantly upregulate cell proliferation, tissue repair and tight junction genes at 2-days post-infection (dpi), compared to WT neonates. Next, to determine if these growth and repair differences persisted later in infection, targeted analysis of repair gene expression and immunofluorescent quantification of pulmonary sealing tight junction molecules ZO-1 and occludin was performed at 6-dpi. Relative to WT neonates, IFNAR-/- neonates had significantly higher whole lung occludin staining and repair gene expression. Together, our data demonstrates IFN-I signaling is extremely pathogenic in the developing lung because by disrupting alveolar repair and pulmonary barrier integrity.

2025-02-22 | GSE287098 | GEO

Loss of tight junction integrity induces loss of epithelial phenotype: case of Claudin11 knock out in testis.

2010-04-11 | GSE15492 | GEO

Loss of tight junction integrity induces loss of epithelial phenotype: case of Claudin11 knock out in testis.

Project description:Epithelium barrier integrity is assumed at least in part by the presence of junctions between cells. Tight-junction formation may be necessary for Sertoli cells to cease dividing and to support germ cell development. Microarray analysis of P20 Cldn11 +/- and Cldn11-/- testes confirmed the impact od Cldn11 deficiency on cell cytoskeleton and junction-related genes. Keywords: transcriptomic analysis Two-condition experiment: P20 Cldn11 +/- vs. P20 Cldn11 -/- testes. A pool of RNA from P20 Cldn11 +/- group was used as the reference group. Each P20 Cldn11 -/- was compared to reference group. Three biological replicates were processed in dye swap.

2010-04-11 | E-GEOD-15492 | biostudies-arrayexpress

Clostridioides difficile toxins deregulate tight junction proteins.

Project description:Clostridioides difficile toxins deregulate tight junction proteins.

| PRJNA973611 | ENA

Membrane prewetting by condensates promotes tight junction belt formation

Project description:Time-resolve proximity proteomics of tight junction. To understand how the tight junction belt is assembled and positioned, we combined APEX2 proximity proteomics of the main junctional scaffold protein ZO-1 with a calcium switch tissue formation assay.This combination allowed us to synchronize the initiation of junction assembly in the entire tissue by the addition of calcium to the culture medium and quantify the time evolution of the junctional proteome during the assembly process using proximity proteomics.

2024-05-22 | PXD052221 | Pride

Tight Junction Claudins-associated vascular heterogeneity determines organotypic metastasis

Project description:Tight Junction Claudins-associated vascular heterogeneity determines organotypic metastasis

| PRJNA818702 | ENA

Interferons disrupt lung epithelial repair during recovery from respiratory infection

Project description:Interferons disrupt lung epithelial repair during recovery from respiratory infection

| PRJNA625478 | ENA

Functional analysis of membrane-associated scaffolding tight junction (TJ) proteins in tumorigenic characteristics of B16-F10 mouse melanoma cells.

Project description:Tight junction (TJ) proteins (Tjps), Tjp1 and Tjp2, are tight junction-associated scaffold proteins that bind to the transmembrane proteins of tight junctions and the underlying cytoskeleton. In this study, we first analyzed the tumorigenic characteristics of B16-F10 melanoma cells, including cell proliferation, migration, invasion, metastatic potential, and the expression patterns of related proteins, after the CRISPR-Cas9-mediated knockout (KO) of Tjp genes. The proliferation of Tjp1 and Tjp2 KO cells significantly increased in vitro. Other tumorigenic characteristics, including migration and invasion, were significantly enhanced in Tjp1 and Tjp2 KO cells.

2024-08-01 | GSE240070 | GEO

Interferons disrupt lung epithelial repair during recovery from respiratory infection [RN19197]

Project description:Interferons disrupt lung epithelial repair during recovery from respiratory infection [RN19197]

| PRJNA625462 | ENA

Interferons disrupt lung epithelial repair during recovery from respiratory infection [RN200717]

Project description:Interferons disrupt lung epithelial repair during recovery from respiratory infection [RN200717]

| PRJNA625463 | ENA