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.

| S-EPMC6124409 | biostudies-literature

Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever

Project description:Typical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems. To identify parameters associated with protection and susceptibility to DHF, we pursued a systems immunology approach integrating plasma chemokine profiling, high-dimensional mass cytometry and peripheral blood mononuclear cell transcriptomic analysis at the onset of fever in a prospective study conducted in Indonesia.

2023-04-13 | GSE215835 | GEO

Systems immunology-based drug repurposing framework to target inflammation in atherosclerosis [Tissue_RNA-seq]

Project description:we present a novel path to drug repurposing to identify new immunotherapies for ASCVD. The integration of time of-flight mass cytometry (CyTOF) and RNA-sequencing identified unique inflammatory signatures in peripheral blood mononuclear cells (PBMCs) stimulated with ASCVD plasma. By comparing these inflammatory signatures to large-scale gene expression data from the LINCS L1000 dataset, we identified drugs that could reverse this inflammatory response. In conclusion, a systems immunology-driven drug repurposing with pre- clinical validation strategy can aid the development of new cardiovascular immunotherapies.

2023-04-23 | GSE230216 | GEO

Systems immunology-based drug repurposing framework to target inflammation in atherosclerosis [DRUG_RNA-seq]

2023-04-23 | GSE230215 | GEO

Systems immunology-based drug repurposing framework to target inflammation in atherosclerosis [RNA-seq_PBMC]

2023-04-23 | GSE230214 | GEO