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Per- and Polyfluoroalkyl Substances Cause Changes in MicroRNA Expression within Extracellular Vesicles

ABSTRACT: Per- and Polyfluoroalkyl Substances Cause Changes in MicroRNA Expression within Extracellular Vesicles

PROVIDER: PRJNA826512 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18745747.fastq.gz	Fastqsanger.gz
	SRR18745748.fastq.gz	Fastqsanger.gz
	SRR18745749.fastq.gz	Fastqsanger.gz
	SRR18745750.fastq.gz	Fastqsanger.gz
	SRR18745751.fastq.gz	Fastqsanger.gz

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Ex Vivo Human Model for Assessing Immunotoxicity of Per- and Polyfluoroalkyl Substances (PFAS)

Project description:Immunotoxicity has emerged as a key health concern for per- and polyfluoroalkyl substances (PFAS), with numerous animal studies showing reduced T-dependent antibody responses (TDAR) and some human epidemiological studies reporting decreased vaccine antibody titers. In recent years, many PFAS have been heavily regulated in Canada; however, with more than 14,000 PFAS and their well-known environmental persistence, evaluating immunotoxicity for each chemical is critical but impractical. This highlights the need for efficient, human-relevant test systems. Here, we assessed immunomodulatory effects of six PFAS analogues using an ex vivo human peripheral blood mononuclear cell (PBMC) model. PBMCs were pre-exposed to PFAS prior to stimulation to mimic environmentally relevant exposure scenarios, in which PFAS exposure precedes an immune challenge. Two immune stimuli were applied, including lipopolysaccharide (LPS) to trigger innate responses and phytohemagglutinin (PHA) to activate T-cell-mediated adaptive pathways. Multiple endpoints were assessed, including cytokine secretion, T-cell proliferation, and transcriptomic alterations. This study found that several PFAS analogues suppressed cytokine secretion and disrupted T-cell proliferation to varying degrees following PHA activation. Transcriptomics results suggest decreased immunoglobulin gene expression, consistent with an immunosuppressive phenotype, although additional validation is required. Overall, the human PBMC model proved to be a cost-effective, ethical, and sensitive new approach method (NAM) that aligned well with prior in vivo data.

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