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Title: Activation of the aryl hydrocarbon receptor during development enhances the pulmonary CD4+ T-cell response to viral infection.

Authors: Boule, Lisbeth A; Winans, Bethany; Lambert, Kris; Vorderstrasse, Beth A; Topham, David J; Pavelka Jr, Martin S; Lawrence, B Paige

Published In Am J Physiol Lung Cell Mol Physiol, (2015 Aug 01)

Abstract: Respiratory infections are a threat to health and economies worldwide, yet the basis for striking variation in the severity of infection is not completely understood. Environmental exposures during development are associated with increased severity and incidence of respiratory infection later in life. Many of these exposures include ligands of the aryl hydrocarbon receptor (AHR), a transcription factor expressed by immune and nonimmune cells. In adult animals, AHR activation alters CD4(+) T cells and changes immunopathology. Developmental AHR activation impacts CD4(+) T-cell responses in lymphoid tissues, but whether skewed responses are also present in the infected lung is unknown. To determine whether pulmonary CD4(+) T-cell responses are modified by developmental AHR activation, mice were exposed to the prototypical AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin during development and infected with influenza virus as adults. Lungs of exposed offspring had greater bronchopulmonary inflammation compared with controls, and activated, virus-specific CD4(+) T cells contributed to the infiltrating leukocytes. These effects were CD4(+) T cell subset specific, with increases in T helper type 1 and regulatory T cells, but no change in the frequency of T helper type 17 cells in the infected lung. This is in direct contrast to prior reports of suppressed conventional CD4(+) T-cell responses in the lymph node. Using adoptive transfers and manipulating the pathogen properties, we determined that developmental exposure influenced factors intrinsic and extrinsic to CD4(+) T cells and may involve developmentally induced changes in signals from infected lung epithelial cells. Thus developmental exposures lead to context-dependent changes in pulmonary CD4(+) T-cell subsets, which may contribute to differential responses to respiratory infection.

PubMed ID: 26071552 Exiting the NIEHS site

MeSH Terms: Animals; CD4-Positive T-Lymphocytes/immunology*; Female; Influenza A virus/immunology; Lymphocyte Activation; Male; Mice, Inbred C57BL; Orthomyxoviridae Infections/immunology*; Orthomyxoviridae Infections/metabolism; Orthomyxoviridae Infections/virology; Receptors, Aryl Hydrocarbon/metabolism*; Respiratory Tract Infections/immunology*; Respiratory Tract Infections/metabolism; Respiratory Tract Infections/virology

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