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

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.