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MiRNA data from C8+ T cells exposed to DCMU or control vehicle (DMSO)

ABSTRACT: DCMU, or diuron, is a widely used herbicide, which can cause adverse effects on human. Here, we develop an approach that combines functional, miRNA and RNA sequencing data to evaluate the effects of DCMU exposure on the human immune system, notably on CD8+ T cells, as the main effectors of the organism’s defense against viruses or neoplastic cells. We found that DCMU reduces T cell abilities, in vitro but also in vivo in orthotopic mouse and zebrafish models, participating to the establishment of a suitable environment for the development of more serious diseases such as cancers. We identified several miRNAs, such as hsa-miR3135b and hsa-miR-21-5p, respectively induced and repressed by DCMU, which alters CD8+ T cell functions. The major advancement of our study is the description of the molecular mechanisms induced by DCMU that control human immune functions.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE189443 | GEO | 2022/07/05

REPOSITORIES: GEO

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Project description:Chemical pollution is a major concern for freshwater ecosystems, but the impact and mechanisms of chemical stressors on communities are barely understood. Pollution stress beyond natural homeostatic capacities can trigger succession of tolerant species within a community, enhancing the overall community tolerance. This process was operationalized in the Pollution-Induced Community Tolerance (PICT) concept and applied in many case studies, however, the molecular mechanisms of community tolerance and implications for ecological functions remain largely unexplored. Our study aimed to demonstrate that 1) community metabolomics can unravel potential mechanisms of PICT in periphyton and 2) induced tolerance helps to maintain primary production under re-occuring pollution. To this end, we grew periphyton for 5 weeks with and without the model herbicide diuron in microcosms, quantified PICT, and determined the related metabolic fingerprint of periphyton by GC–MS-based untargeted metabolomics. Further, we explored the autotrophic community based on pigment composition and functional parameters including photosynthesis and gross primary production. Chronic diuron exposure resulted in a shift in pigment composition, higher community tolerance and an individual metabolic fingerprint in the contaminated communities. Opposing responses of selected metabolites during a short-term exposure indicated differences in diuron pre-adaptation in the different communities. Metabolites (threonic acid and two sugar acid lactones) were found to be related to tolerance development, suggesting that ascorbate metabolism was induced in contaminated communities. Despite these compensating mechanism, contaminated communities were compromised in production-to-respiration ratio and biomass. A ranking of sensitivity thresholds of different biological endpoints revealed that metabolites were less sensitive than photosynthetic parameters, which reflects the mode-of-action of the herbicide. In conclusion, we could demonstrate that community metabolomics is able to unravel complex biochemical changes and allows mechanistic insights into community tolerance. Moreover, we were able to show that induced community tolerance was insufficient to safeguard functions like primary production.

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MiRNA data from C8+ T cells exposed to DCMU or control vehicle (DMSO)

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