title: In utero arsenic exposure and fetal immune repertoire in a US pregnancy cohort.
abstract: Arsenic has wide-ranging effects on human health and there is evidence that it alters the immune response by influencing CD4+/CD8+ T cell ratios, IL-2 cytokine levels, and the expression of immune-response genes. We investigated the impact of in utero environmental arsenic exposure on immune development and function in newborns participating in a pregnancy cohort in New Hampshire, U.S., where arsenic levels have exceeded the current EPA maximum contaminant level of 10 μg/L. Our results showed that maternal urinary arsenic concentrations were inversely related to absolute total CD45RA+ CD4+ cord blood CD69+ T cell counts (N=116, p=0.04) and positively associated with CD45RA+ CD69- CD294+ cell counts (p=0.01). In placental samples (N=70), higher in utero urinary arsenic concentrations were positively associated with the expression of IL1β (p=0.03). These data provide evidence that relatively low-level arsenic exposure in utero may alter the fetal immune system and lead to immune dysregulation.
authors.affiliation: Division of Immunology and Allergy, Stanford University, 730 Welch Road, Stanford, CA, USA. Electronic address: Knadeau@stanford.edu.
authors.forename: Kari C
authors.initials: KC
authors.lastname: Nadeau
authors.affiliation: Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH 03755, USA. Electronic address: Zhigang.Li@Dartmouth.edu.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH 03755, USA. Electronic address: Shohreh.F.Farzan@Dartmouth.edu.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Farzan
authors.affiliation: Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH 03755, USA. Electronic address: Devin.C.Koestler@Dartmouth.edu.
authors.forename: Devin
authors.initials: D
authors.lastname: Koestler
authors.affiliation: University of Miami, Miller School of Medicine, 1600 NW 10th Ave #1140, Miami, FL 33136, USA. Electronic address: drobbins@med.miami.edu.
authors.forename: David
authors.initials: D
authors.lastname: Robbins
authors.affiliation: University of Miami, Miller School of Medicine, 1600 NW 10th Ave #1140, Miami, FL 33136, USA. Electronic address: dlfei@med.miami.edu.
authors.forename: Dennis Liang
authors.initials: DL
authors.lastname: Fei
authors.affiliation: Institute for Immunity, Transplantation, and Infection, Stanford University, 299 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Malipatlolla
authors.affiliation: Institute for Immunity, Transplantation, and Infection, Stanford University, 299 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Holden
authors.initials: H
authors.lastname: Maecker
authors.affiliation: Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH 03755, USA. Electronic address: Richard.I.Enelow@Dartmouth.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Enelow
authors.affiliation: Brigham and Women's Hospital, Department of Medicine, Channing Division of Network Medicine, Harvard Medical School, 181 Longwood Ave, Boston, MA 02115, USA; Harvard School of Public Health, Department of Environmental Health, 677 Huntington Ave, Boston, MA 02115, USA. Electronic address: susan.korrick@channing.harvard.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Korrick
authors.affiliation: Geisel School of Medicine at Dartmouth, 1 Rope Ferry Road, Hanover, NH 03755, USA. Electronic address: Margaret.R.Karagas@Dartmouth.edu.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
mesh_terms: D000328:Adult; D001151:Arsenic / Q000009:adverse effects*; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000502:physiology*; D016130:Immunophenotyping; D007231:Infant, Newborn; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009513:New Hampshire; D010641:Phenotype; D010920:Placenta / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D001151:Arsenic
keywords: AQP9; Arsenic; IL1β; Immune function; In utero; T cell