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Focusing on the AhR: a potential mechanism for immune effects of prenatal exposures.

Konkel L - Environ. Health Perspect. (2014)

View Article: PubMed Central - PubMed

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Epidemiological studies suggest that prenatal and early-life exposures to certain chemicals can influence immune system function later in life... In this issue of EHP, researchers report an altered immune response to influenza virus infection in adult mice that had been exposed prenatally to 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD), revealing a novel cellular target of developmental exposures. “Researchers have been demonstrating for a number of years that the developing immune system is uniquely sensitive to chemical exposures,” says Dori Germolec, leader of the Systems Toxicology Group at the National Institute of Environmental Health Sciences. “This study provides a mechanistic framework that may help us understand why this is the case. ” Germolec was not involved in the current study... Previous epidemiological studies have reported that maternal and cord blood levels of polychlorinated biphenyls and dioxins corresponded with decreased immune response to routine vaccinations and increased respiratory infections in children... At age 6–8 weeks, the adult offspring were infected with influenza A virus... CD4 T cells have the ability to differentiate into distinct subsets of immune cells in response to infection... Paige Lawrence, an immunotoxicologist at the University of Rochester, “we saw an increase in the proportion of regulatory T cells, which put the brakes on an immune response. ” To test whether developmental exposure to TCDD caused intrinsic changes in the ability of CD4 T cells to differentiate, the researchers transferred purified cells from exposed offspring into unexposed mice... They observed a reduction in the number of T helper cells responding to influenza virus infection when the cells came from exposed mice... Future studies will explore whether changes in immune function can be transferred to future generations of offspring. “The idea that you can expose a pregnant mouse to an environmental chemical like a dioxin during pregnancy and have that adversely impact the immune response [of its offspring] to influenza later in life has profound consequences for public health,” says Michael Laiosa, an environmental health scientist from the Zilber School of Public Health, University of Wisconsin–Milwaukee, who was not involved in the study... Laiosa notes it’s not clear whether all chemicals that bind the AhR would have the same effect as TCDD, which is one of the most potent agents known to act on that receptor... This new work “has implications for examining how early-life exposures affect immune function in the human population, where antibody responses are often the sole measurement,” the authors wrote... Indeed, Lawrence now hopes to turn this new knowledge toward studying human populations... She says, “This tells us we should also be looking more closely at the function of different cell types and what those cells contribute to the immune response—not just measuring the level of antibodies produced. ”

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A new study of influenza A (shown) and TCDD provides a mechanistic framework that may help researchers understand how certain chemical exposures affect the developing immune system.© Eye of Science/Science Source
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d35e98: A new study of influenza A (shown) and TCDD provides a mechanistic framework that may help researchers understand how certain chemical exposures affect the developing immune system.© Eye of Science/Science Source


Focusing on the AhR: a potential mechanism for immune effects of prenatal exposures.

Konkel L - Environ. Health Perspect. (2014)

A new study of influenza A (shown) and TCDD provides a mechanistic framework that may help researchers understand how certain chemical exposures affect the developing immune system.© Eye of Science/Science Source
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4216157&req=5

d35e98: A new study of influenza A (shown) and TCDD provides a mechanistic framework that may help researchers understand how certain chemical exposures affect the developing immune system.© Eye of Science/Science Source

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Epidemiological studies suggest that prenatal and early-life exposures to certain chemicals can influence immune system function later in life... In this issue of EHP, researchers report an altered immune response to influenza virus infection in adult mice that had been exposed prenatally to 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD), revealing a novel cellular target of developmental exposures. “Researchers have been demonstrating for a number of years that the developing immune system is uniquely sensitive to chemical exposures,” says Dori Germolec, leader of the Systems Toxicology Group at the National Institute of Environmental Health Sciences. “This study provides a mechanistic framework that may help us understand why this is the case. ” Germolec was not involved in the current study... Previous epidemiological studies have reported that maternal and cord blood levels of polychlorinated biphenyls and dioxins corresponded with decreased immune response to routine vaccinations and increased respiratory infections in children... At age 6–8 weeks, the adult offspring were infected with influenza A virus... CD4 T cells have the ability to differentiate into distinct subsets of immune cells in response to infection... Paige Lawrence, an immunotoxicologist at the University of Rochester, “we saw an increase in the proportion of regulatory T cells, which put the brakes on an immune response. ” To test whether developmental exposure to TCDD caused intrinsic changes in the ability of CD4 T cells to differentiate, the researchers transferred purified cells from exposed offspring into unexposed mice... They observed a reduction in the number of T helper cells responding to influenza virus infection when the cells came from exposed mice... Future studies will explore whether changes in immune function can be transferred to future generations of offspring. “The idea that you can expose a pregnant mouse to an environmental chemical like a dioxin during pregnancy and have that adversely impact the immune response [of its offspring] to influenza later in life has profound consequences for public health,” says Michael Laiosa, an environmental health scientist from the Zilber School of Public Health, University of Wisconsin–Milwaukee, who was not involved in the study... Laiosa notes it’s not clear whether all chemicals that bind the AhR would have the same effect as TCDD, which is one of the most potent agents known to act on that receptor... This new work “has implications for examining how early-life exposures affect immune function in the human population, where antibody responses are often the sole measurement,” the authors wrote... Indeed, Lawrence now hopes to turn this new knowledge toward studying human populations... She says, “This tells us we should also be looking more closely at the function of different cell types and what those cells contribute to the immune response—not just measuring the level of antibodies produced. ”

Show MeSH
Related in: MedlinePlus