RECETOX, Faculty of Science, Masaryk University, Kotlářská 2, 602 00 Brno, Czech Republic.
Department of Physiological Sciences and Center for Environmental and Human Toxicology, UF Genetics Institute, College of Veterinary Medicine, University of Florida, Gainesville, Florida 32611, United States.
Environ Sci Technol. 2024 Jan 9;58(1):90-98. doi: 10.1021/acs.est.3c05109. Epub 2023 Dec 19.
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.
虽然流行病学研究（例如疫苗接种后抗体反应受抑制）描述了全氟和多氟烷基物质（PFAS）的免疫调节作用，但潜在机制仍未完全阐明。为了揭示 PFAS 暴露对免疫的作用机制，我们研究了外周血单个核细胞（PBMC）对 PFAS 暴露（具体为 PFPA、PFOA、PFNA、PFDA、PFUnDA、PFHxS 和 PFOS 暴露）的全基因组转录组变化。在横断面 CELSPAC：青年成年人研究中分析了血液样本和血液中的化学负荷。该研究的总体目标是确定对多种 PFAS 化学品具有敏感性的基因集和保守的细胞途径。多种 PFAS 暴露（即血液中至少有四种 PFAS 的水平）扰乱了与适应性免疫有关的转录组网络。具体而言，与晚期 B 细胞发育紧密相关的过程，如 B 细胞受体信号转导、生发中心反应和浆细胞发育，被证明受到影响。我们的综合转录组分析确定了 B 细胞发育的中断，特别是对分泌抗体细胞的成熟的影响，作为 PFAS 免疫毒性的潜在机制。
