Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Developmental Activation of the AHR Increases Effector CD4+ T Cells and Exacerbates Symptoms in Autoimmune Disease-Prone Gnaq+/- Mice.

Authors: Boule, Lisbeth A; Burke, Catherine G; Fenton, Bruce M; Thevenet-Morrison, Kelly; Jusko, Todd A; Lawrence, B Paige

Published In Toxicol Sci, (2015 Dec)

Abstract: Perinatal environmental exposures are potentially important contributors to the increase in autoimmune diseases. Yet, the mechanisms by which these exposures increase self-reactive immune responses later in life are poorly understood. Autoimmune diseases require CD4(+) T cells for initiation, progression, and/or clinical symptoms; thus, developmental exposures that cause durable changes in CD4(+) T cells may play a role. Early life activation of the aryl hydrocarbon receptor (AHR) causes persistent changes in the response of CD4(+) T cells to infection later in life but whether CD4(+) T cells are affected by developmental exposure in the context of an autoimmune disease is unknown. Gnaq(+/-) mice develop symptoms of autoimmune disease similar to those measured clinically, and therefore can be used to evaluate gene-environment interactions during development on disease progression. Herein, we examined the effect of AHR activation in utero and via lactation, or solely via lactation, on disease onset and severity in adult Gnaq(+/-) offspring. Developmental activation of the AHR-accelerated disease in Gnaq(+/-) mice, and this correlates with increases in effector CD4(+) T-cell populations. Increased symptom onset and cellular changes due to early life AHR activation were more evident in female Gnaq(+/-) mice compared with males. These observations suggest that developmental AHR activation by pollutants, and other exogenous ligands, may increase the likelihood that genetically predisposed individuals will develop clinical symptoms of autoimmune disease later in life.

PubMed ID: 26363170 Exiting the NIEHS site

MeSH Terms: Age Factors; Animals; Autoimmune Diseases/chemically induced*; Autoimmune Diseases/enzymology; Autoimmune Diseases/genetics; Autoimmune Diseases/immunology; Autoimmunity*; Basic Helix-Loop-Helix Transcription Factors/agonists*; Basic Helix-Loop-Helix Transcription Factors/metabolism; CD4-Positive T-Lymphocytes/enzymology*; CD4-Positive T-Lymphocytes/immunology; Environmental Pollutants/toxicity*; Female; GTP-Binding Protein alpha Subunits, Gq-G11/deficiency*; GTP-Binding Protein alpha Subunits, Gq-G11/genetics; Gene-Environment Interaction; Genetic Predisposition to Disease; Gestational Age; Male; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Polychlorinated Dibenzodioxins/toxicity*; Pregnancy; Prenatal Exposure Delayed Effects; Receptors, Aryl Hydrocarbon/agonists*; Receptors, Aryl Hydrocarbon/metabolism; Risk Factors; Severity of Illness Index; Sex Factors

Back
to Top