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ToxSci Advance Access published online on November 17, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm283
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The aryl hydrocarbon receptor affects distinct tissue compartments during ontogeny of the immune system

Jason P. Hogaboam1,#, Amanda J. Moore2,# and B. Paige Lawrence1,2,*

1 Department of Pharmaceutical Sciences, Center for Reproductive Biology and Biotechnology Training Program, Washington State University, Pullman, WA 99164 2 Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642

* To whom correspondence should be addressed: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, 575 Elmwood Ave, Box 850, Rochester, NY 14642. Tel: 585-275-1974; Fax: 585-276-0239; Email: paige_lawrence{at}urmc.rochester.edu

Received September 21, 2007; revision received November 8, 2007; accepted November 12, 2007


  Abstract

There is growing evidence that prenatal and early post-natal environmental factors influence the development and programming of the immune system, causing long-lasting negative health consequences. The aryl hydrocarbon receptor (AhR) is an important modulator of the development and function of the immune system; however, the mechanism is poorly understood. Exposure to the AhR agonist TCDD throughout gestation and during lactation yields adult offspring with persistent defects in their immune response to influenza virus. These functional alterations include suppressed lymphocyte responses and increased inflammation in the infected lung despite normal cellularity and anatomical development of lymphoid organs. The studies presented here were conducted to determine the critical period during immune ontogeny that is particularly sensitive to inappropriate AhR activation. We also investigated the contribution of AhR-mediated events within and extrinsic to hematopoietic cells. Our findings show that AhR activation alters different elements of the immune system at different times during development by affecting different tissue targets. In particular, diminished T cell responses arise due to deregulated events within bone marrow derived cells. In contrast, increased IFN{gamma} levels in the infected lung result from AhR-regulated events extrinsic to bone marrow derived cells, and require AhR agonist exposure during early gestation. The persistence of AhR activation induced immune modulation was also compared, revealing that AhR activation causes long-lasting functional alterations in the developing immune system, whereas the impact on the mature immune system is transient.

# JPH and AJM contributed equally to the experimental work presented


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