title: Does developmental exposure to perflurooctanoic acid (PFOA) induce immunopathologies commonly observed in neurodevelopmental disorders?
abstract: Immune comorbidities often are reported in subsets of patients with neurodevelopmental disorders, including autism spectrum disorders and attention-deficit hyperactivity disorder. A common immunopathology is an increase in serum autoantibodies against myelin basic protein (MBP) relative to control patients. Increases in autoantibodies suggest possible deficits in self-tolerance that may contribute to the formation of brain-specific autoantibodies and subsequent effects on the central nervous system (CNS). Oppositely, the formation of neuronal autoantibodies may be a reaction to neuronal injury or damage. Perfluorooctanoic acid (PFOA) is an environmental pollutant that induces multisystem toxicity in rodent models, including immunotoxicity and neurotoxicity. We hypothesized that developmental exposure to PFOA may induce immunotoxicity similar to that observed in subsets of patients with neurodevelopmental disorders. To test this hypothesis, we evaluated subsets of T cells from spleens, serum markers of autoreactivity, and levels of MBP and T cell infiltration in the cerebella of adult offspring exposed to 0.02, 0.2, or 2mg/kg of PFOA given to dams from gestation through lactation. Litter weights of offspring from dams exposed to 2mg/kg of PFOA were reduced by 32.6%, on average, from postnatal day one (PND1) through weaning (PND21). The percentage of splenic CD4+CD25+Foxp3+ T cells in male and female offspring from dams exposed to 2mg/kg of PFOA was reduced by 22% relative to the control percentage. Ex vivo co-cultures of splenic CD4+CD25+ T cells and CD4+CD25- T cells from dosed male offspring produced less IL-10 relative to control cells. Anti-ssDNA, a serum marker of autoreactivity, was decreased by 26%, on average, in female offspring from dams exposed to 0.02 and 2mg/kg PFOA. No other endpoints were statistically different by dose. These data suggest that developmental PFOA exposure may impact T cell responses and may be a possible route to downstream effects on other systems.
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
authors.forename: Qing
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
authors.forename: Jason N
authors.initials: JN
authors.lastname: Franklin
authors.affiliation: Department of Biology, East Carolina University, Greenville, NC, United States; Department of Chemistry, East Carolina University, Greenville, NC, United States.
authors.forename: Ian
authors.initials: I
authors.lastname: Bryan
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
authors.forename: Erin
authors.initials: E
authors.lastname: Morris
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wood
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC, United States. Electronic address: dewittj@ecu.edu.
authors.forename: Jamie C
authors.initials: JC
authors.lastname: DeWitt
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002210:Caprylates / Q000633:toxicity*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005865:Gestational Age; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007774:Lactation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013154:Spleen / Q000187:drug effects / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D015415:Biomarkers; D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D004676:Myelin Basic Protein; D016753:Interleukin-10; C023036:perfluorooctanoic acid