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Epigenetic underpinnings of developmental immunotoxicity and autoimmune disease.

ABSTRACT: The concordance rate for developing autoimmune disease in identical twins is around 50% demonstrating that gene and environmental interactions contribute to disease etiology. The environmental contribution to autoimmune disease is a wide-ranging concept including exposure to immunotoxic environmental chemicals. Because the immune system is immature during development suggests that adult-onset autoimmunity may originate when the immune system is particularly sensitive. Among the pollutants most closely associated with inflammation and/or autoimmunity include Bisphenol-A, mercury, TCDD, and trichloroethylene. These toxicants have been shown to impart epigenetic changes (e.g., DNA methylation) that may alter immune function and promote autoreactivity. Here we review these autoimmune-promoting toxicants and their relation to immune cell epigenetics both in terms of adult and developmental exposure.

SUBMITTER: Blossom SJ

PROVIDER: S-EPMC6319940 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

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Epigenetic underpinnings of developmental immunotoxicity and autoimmune disease.

Blossom Sarah J SJ Gilbert Kathleen M KM

Current opinion in toxicology 20171201

The concordance rate for developing autoimmune disease in identical twins is around 50% demonstrating that gene and environmental interactions contribute to disease etiology. The environmental contribution to autoimmune disease is a wide-ranging concept including exposure to immunotoxic environmental chemicals. Because the immune system is immature during development suggests that adult-onset autoimmunity may originate when the immune system is particularly sensitive. Among the pollutants most c ...[more]

PMID: 30613805

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Project description:Innate differences in human temperament strongly influence how individuals cope with stress and predispose for specific types of psychopathology. The present study examines the developing brain in an animal model of temperamental differences to understand how altered neurodevelopment may engender differences in emotional reactivity that are stable throughout the animal’s life. We utilize selectively-bred High Responder (bHR) and Low Responder (bLR) rats that exhibit dramatic emotional behavior differences, with bHRs exhibiting exaggerated novelty-exploration, aggression, impulsivity and drug self-administration, and bLRs showing marked behavioral inhibition, exaggerated anxiety- and depressive-like behavior. Using Affymetrix microarrays, we assessed bLR/bHR gene expression in the developing brain on postnatal days (P)7, 14, and 21, focusing on the hippocampus and nucleus accumbens, two regions related to emotionality and known to differ in adult bLR/bHR rats. We found dramatic bLR/bHR gene expression differences in the P7 and P14 hippocampus, with minimal differences in the nucleus accumbens. Some of the most profound differences involved genes critical for neurodevelopment and synaptogenesis. Stereological studies evaluated hippocampal structure in developing bHR/bLR pups, revealing enhanced hippocampal volume and cell proliferation in bLR animals. Finally, behavioral studies showed that the bHR/bLR behavioral phenotypes emerge very early in life, with exploratory differences apparent at P16 and anxiety differences present by P25. Together these data point to specific brain regions and critical periods when the bHR/bLR phenotypes begin to diverge, which may eventually allow us to test possible therapeutic interventions to normalize extreme phenotypes (e.g. the anxiety-prone nature of bLRs or drug addiction proclivity of bHRs). 2x2x3 factorial design with N=6 per group. Factors as follows: 1) Two selectively bred strains of rats (derived from an original Sprague Dawley population) termed High Responders (HR) and Low Responders (LR), 2) Two brain regions, Hippocampus (HPC) and Nucleus Accumbens (N.Acc), 3) Three developmental timepoints, specifically postnatal days 7 (P7), 14 (P14) and 21 (P21).

Dataset Information

Epigenetic underpinnings of developmental immunotoxicity and autoimmune disease.

Publications

Epigenetic underpinnings of developmental immunotoxicity and autoimmune disease.

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