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A novel systems immunology approach identifies the collective impact of five miRNAs in Th2 inflammation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus synthetic construct

PROVIDER: GSE109737 | GEO | 2018/06/18

REPOSITORIES: GEO

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A novel systems immunology approach identifies the collective impact of five miRNAs in Th2 inflammation (microRNA)

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A novel systems immunology approach identifies the collective impact of five miRNAs in Th2 inflammation (mRNA)

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A systems immunology approach identifies the collective impact of 5 miRs in Th2 inflammation.

Project description:Allergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including microRNAs (miRs), are pivotal in maintaining immune homeostasis. Since an altered expression of various miRs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRs control mechanisms ensuring Th2 stability and maintenance in the lung. We isolated murine CD4+ Th2 cells from allergic inflamed lungs and profiled gene and miR expression. Instead of focusing on the magnitude of miR differential expression, here we addressed the secondary consequences for the set of molecular interactions in the cell, the interactome. We developed the Impact of Differential Expression Across Layers, a network-based algorithm to prioritize disease-relevant miRs based on the central role of their targets in the molecular interactome. This method identified 5 Th2-related miRs (mir27b, mir206, mir106b, mir203, and mir23b) whose antagonization led to a sharp reduction of the Th2 phenotype. Overall, a systems biology tool was developed and validated, highlighting the role of miRs in Th2-driven immune response. This result offers potentially novel approaches for therapeutic interventions.

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A novel systems immunology approach identifies the collective impact of five miRNAs in Th2 inflammation

Project description:A novel systems immunology approach identifies the collective impact of five miRNAs in Th2 inflammation

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A novel systems immunology approach identifies the collective impact of five miRNAs in Th2 inflammation (microRNA)

Project description:A novel systems immunology approach identifies the collective impact of five miRNAs in Th2 inflammation (microRNA)

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