The DCMU Herbicide Shapes T-cell Functions By Modulating Micro-RNA Expression Profiles.

Autor:	Autin P; Nantes Université, INSERM UMR1307, CNRS UMR6075, Université d'Angers, CRCI2NA, Nantes, France., Deshayes S; Nantes Université, INSERM UMR1307, CNRS UMR6075, Université d'Angers, CRCI2NA, Nantes, France., Lea J; Université de Rennes, ImPACcell Plateform, BIOSIT, Rennes, France., Boisgerault N; Nantes Université, INSERM UMR1307, CNRS UMR6075, Université d'Angers, CRCI2NA, Nantes, France., Dupré E; Nantes Université, Univ Angers, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302/EMR6001, Nantes, France., Labarrière N; Nantes Université, Univ Angers, INSERM, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302/EMR6001, Nantes, France., Leguevel R; Université de Rennes, ImPACcell Plateform, BIOSIT, Rennes, France., Fonteneau JF; Nantes Université, INSERM UMR1307, CNRS UMR6075, Université d'Angers, CRCI2NA, Nantes, France., Blanquart C; Nantes Université, INSERM UMR1307, CNRS UMR6075, Université d'Angers, CRCI2NA, Nantes, France., Fradin D; Nantes Université, INSERM UMR1307, CNRS UMR6075, Université d'Angers, CRCI2NA, Nantes, France.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jul 28; Vol. 13, pp. 925241. Date of Electronic Publication: 2022 Jul 28 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.925241
Abstrakt:	DCMU [N-(3,4-dichlorophenyl)-N-dimethylurea] or diuron is a widely used herbicide, which can cause adverse effects on human, especially on immune cells, due to their intrinsic properties and wide distribution. These cells are important for fighting not only against virus or bacteria but also against neoplastic cell development. We developed an approach that combines functional studies and miRNA and RNA sequencing data to evaluate the effects of DCMU on the human immune response against cancer, particularly the one carried out by CD8+ T cells. We found that DCMU modulates the expression of miRNA in a dose-dependent manner, leading to a specific pattern of gene expression and consequently to a diminished cytokine and granzyme B secretions. Using mimics or anti-miRs, we identified several miRNA, such as hsa-miR-3135b and hsa-miR-21-5p, that regulate these secretions. All these changes reduce the CD8+ T cells' cytotoxic activity directed against cancer cells, in vitro and in vivo in a zebrafish model. To conclude, our study suggests that DCMU reduces T-cell abilities, participating thus to the establishment of an environment conducive to cancer development. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Autin, Deshayes, Lea, Boisgerault, Dupré, Labarrière, Leguevel, Fonteneau, Blanquart and Fradin.)
Databáze:	MEDLINE
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