Altered Transcriptome Response in PBMCs of Czech Adults Linked to Multiple PFAS Exposure: B Cell Development as a Target of PFAS Immunotoxicity

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Authors

RUDZANOVÁ Barbora THON Vojtěch VESPALCOVÁ Hana MARTYNIUK Christopher J. PILER Pavel ZVONAŘ Martin KLÁNOVÁ Jana BLÁHA Luděk ADAMOVSKÝ Ondřej

Year of publication 2024
Type Article in Periodical
Magazine / Source ENVIRONMENTAL SCIENCE & TECHNOLOGY
MU Faculty or unit

Faculty of Science

Citation
Web https://pubs.acs.org/doi/10.1021/acs.est.3c05109
Doi http://dx.doi.org/10.1021/acs.est.3c05109
Keywords Perfluoroalkyl substances; gene expression; peripheral blood mononuclear cells; adult cohort; transcriptomics; immunotoxicity; B cell; plasma cell
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Description While the immunomodulation effects of per- and polyfluoroalkyl substances (PFASs) are described on the level of clinical signs in epidemiological studies (e.g., suppressed antibody response after vaccination), the underlying mechanism has still not been fully elucidated. To reveal mechanisms of PFAS exposure on immunity, we investigated the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMCs) responding to PFAS exposure (specifically, exposure to PFPA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS). Blood samples and the chemical load in the blood were analyzed under the cross-sectional CELSPAC: Young Adults study. The overall aim of the study was to identify sensitive gene sets and cellular pathways conserved for multiple PFAS chemicals. Transcriptome networks related to adaptive immunity were perturbed by multiple PFAS exposure (i.e., blood levels of at least four PFASs). Specifically, processes tightly connected with late B cell development, such as B cell receptor signaling, germinal center reactions, and plasma cell development, were shown to be affected. Our comprehensive transcriptome analysis identified the disruption of B cell development, specifically the impact on the maturation of antibody-secreting cells, as a potential mechanism underlying PFAS immunotoxicity.
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