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Perfluoroalkyl substances (PFASs) decrease the expression of recombination-activating genes (RAG1 and RAG2) in human

Aafke W F Janssen1, Jochem Louisse2, Deborah Rijkers2

  • 1Wageningen Food Safety Research (WFSR), Wageningen University and Research, Akkermaalsbos 2, 6708 WB, Wageningen, The Netherlands. aafke.janssen@wur.nl.

Archives of Toxicology
|November 3, 2022
PubMed
Summary

Per- and polyfluoroalkyl substances (PFASs) impact B cell function by decreasing expression of RAG1 and RAG2. This study ranks PFASs by potency, revealing potential mechanisms for PFAS-induced immunotoxicity.

Keywords:
ImmunotoxicityNamalwa cellsPFASsRNA sequencing

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Area of Science:

  • Environmental Health
  • Toxicology
  • Immunology

Background:

  • Per- and polyfluoroalkyl substances (PFASs) are widespread environmental contaminants linked to various toxicities.
  • Limited understanding exists regarding the mechanisms of PFAS-induced immunotoxicity, particularly effects on B cells.

Purpose of the Study:

  • To investigate the impact of PFASs on human B cell function.
  • To identify specific genes and pathways affected by PFAS exposure in B cells.
  • To determine the relative potency of different PFASs in affecting B cell gene expression.

Main Methods:

  • RNA sequencing (RNA-seq) analysis of human Namalwa B cells exposed to PFOA.
  • Ingenuity Pathway Analysis (IPA) to interpret gene expression changes.
  • RT-qPCR to quantify RAG1 and RAG2 expression after exposure to PFOA, PFNA, PFHxS, and PFOS.
  • Concentration-response modeling using PROAST software.

Main Results:

  • PFOA exposure altered gene expression related to B cell development and primary immunodeficiency signaling.
  • PFOA significantly decreased the expression of RAG1 and RAG2, critical for V(D)J recombination.
  • A potency ranking for RAG1/RAG2 downregulation was established: PFNA > PFOA > PFOS > PFHxS.

Conclusions:

  • PFASs can affect B cell function by downregulating RAG1 and RAG2 expression.
  • These genes represent potential molecular targets mediating PFAS immunotoxicity.
  • The findings provide in vitro insights into PFAS-induced immunotoxic mechanisms.