{"doi":"10.1289/ehp16726","title":"In utero per – and polyfluoroalkyl substances (PFAS) exposure and changes in infant T helper cell development among UPSIDE-ECHO cohort participants.","abstract":"BACKGROUND: Environmental exposures to toxicants, such as per- and polyfluoroalkyl substances (PFAS), during gestation can disrupt immune development, causing long-term impacts on a child's ability to generate a well-regulated, protective immune response. T-cells coordinate with all immune cell types to orchestrate both cellular and antibody-mediated responses. While there is compelling evidence that PFAS alters immunity in humans, the specific effects of early life PFAS exposure on infant T-cell development are unreported. Because of their central role in immunity, altered T-cell development in infants would have implications on immune responses broadly and long-term. OBJECTIVES: We seek to model longitudinal changes in the frequency of functionally distinct CD4+ T-cell subpopulations from birth through 12 months and their association with in-utero PFAS exposure. METHODS: Maternal-infant dyads were recruited as part of the UPSIDE-ECHO cohort during the first trimester between 2015 and 2019 in Rochester, New York; dyads were followed through the infant's first birthday. Maternal PFAS concentrations (PFOS, PFOA, PFNA, PFHXS and PFDA) were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6- and 12-months using mass cytometry and high-dimensional clustering methods. Linear mixed-effects models were employed to analyze the relationship between maternal PFAS concentrations and CD4+ T-cell subpopulations (n=200). All models included a PFAS and age interaction and were adjusted for parity, infant sex, and pre-pregnancy body mass index. RESULTS: -unit increase in PFOS was associated with lower Tfh [0.17% (95%CI: -0.30, -0.40)] and greater Th2 [0.27% (95%CI: 0.18, 0.35)] cell percentages at 12 months. Similar trends were observed for PFOA, PFNA, PFHXS and PFDA. TEXT. DISCUSSION: Maternal PFAS exposures correlate with cell-specific changes in the infant T-cell compartment, including key CD4+ T-cell subpopulations that play central roles in coordinating well-regulated, protective immunity. Future studies into the role of PFAS-associated T-cell distribution and risk of adverse immune-related health outcomes in children are warranted. https://doi.org/10.1289/EHP16726.","journal":"Environmental Health Perspectives","year":2025,"id":521372,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9687,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":530046,"name":"Nathan Laniewski","orcid":"0000-0002-9550-8872","position":1,"is_corresponding":false},{"id":513460,"name":"Todd A. Jusko","orcid":"0000-0002-3194-6718","position":2,"is_corresponding":false},{"id":368417,"name":"Xing Qiu","orcid":"0000-0002-2330-3544","position":3,"is_corresponding":false},{"id":394474,"name":"B. Paige Lawrence","orcid":"0000-0003-4882-9750","position":4,"is_corresponding":false},{"id":332121,"name":"Zorimar Rivera‐Núñez","orcid":"0000-0002-0718-1807","position":5,"is_corresponding":false},{"id":661945,"name":"Jessica Brunner","orcid":"0009-0003-3882-1138","position":6,"is_corresponding":false},{"id":662684,"name":"Meghan Best","orcid":null,"position":7,"is_corresponding":false},{"id":662687,"name":"Allison Macomber","orcid":null,"position":8,"is_corresponding":false},{"id":1392217,"name":"A S St Leger","orcid":null,"position":9,"is_corresponding":false},{"id":291977,"name":"Kurunthachalam Kannan","orcid":"0000-0002-1926-7456","position":10,"is_corresponding":false},{"id":661950,"name":"Richard K. Miller","orcid":"0000-0002-6691-7538","position":11,"is_corresponding":false},{"id":228378,"name":"Emily S. Barrett","orcid":"0000-0001-9463-524X","position":12,"is_corresponding":false},{"id":271737,"name":"Thomas G. O’Connor","orcid":"0000-0002-8590-5057","position":13,"is_corresponding":false},{"id":436587,"name":"Kristin Scheible","orcid":"0000-0002-7879-8222","position":14,"is_corresponding":false},{"id":1391700,"name":"Darline Castro Meléndez","orcid":"0000-0001-9743-833X","position":0,"is_corresponding":true}],"reference_count":119,"raw_metadata":null,"created_at":"2026-07-19T02:49:44.558743Z","pmid":"40489731","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}