tetano
Editor, Senior Moderator
Am J Physiol Lung Cell Mol Physiol. 2015 Jun 12:ajplung.00135.2015. doi: 10.1152/ajplung.00135.2015. [Epub ahead of print]
[h=1]Activation of the aryl hydrocarbon receptor during development enhances the pulmonary CD4+ T cell response to viral infection.[/h] Boule LA[SUP]1[/SUP], Winans B[SUP]1[/SUP], Lambert K[SUP]1[/SUP], Vorderstrasse BA[SUP]2[/SUP], Topham DJ[SUP]1[/SUP], Pavelka MS Jr[SUP]1[/SUP], Lawrence BP[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 non-immune cells. In adult animals, AHR activation alters CD4[SUP]+[/SUP] T-cells and changes immunopathology. Developmental AHR activation impacts CD4[SUP]+[/SUP] T-cell responses in lymphoid tissues, but whether skewed responses are also present in the infected lung is unknown. To determine if pulmonary CD4[SUP]+[/SUP] T-cell responses are modified by developmental AHR activation, mice were exposed to the prototypical AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during development and infected with influenza virus as adults. Lungs of exposed offspring had greater bronchopulmonary inflammation compared to controls, and activated, virus-specific CD4[SUP]+[/SUP] T-cells contributed to the infiltrating leukocytes. These effects were CD4[SUP]+[/SUP] T-cell-subset specific, with increases in Th1 and regulatory T cells, but no change in the frequency of Th17 cells in the infected lung. This is in direct contrast with prior reports of suppressed conventional CD4[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] T-cell subsets, which may contribute to differential responses to respiratory infection.
Copyright ? 2015, American Journal of Physiology - Lung Cellular and Molecular Physiology.
[h=4]KEYWORDS:[/h] CD4 T cell; aryl hydrocarbon receptor; developmental exposure; influenza virus; respiratory infection
PMID: 26071552 [PubMed - as supplied by publisher]
[h=1]Activation of the aryl hydrocarbon receptor during development enhances the pulmonary CD4+ T cell response to viral infection.[/h] Boule LA[SUP]1[/SUP], Winans B[SUP]1[/SUP], Lambert K[SUP]1[/SUP], Vorderstrasse BA[SUP]2[/SUP], Topham DJ[SUP]1[/SUP], Pavelka MS Jr[SUP]1[/SUP], Lawrence BP[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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 non-immune cells. In adult animals, AHR activation alters CD4[SUP]+[/SUP] T-cells and changes immunopathology. Developmental AHR activation impacts CD4[SUP]+[/SUP] T-cell responses in lymphoid tissues, but whether skewed responses are also present in the infected lung is unknown. To determine if pulmonary CD4[SUP]+[/SUP] T-cell responses are modified by developmental AHR activation, mice were exposed to the prototypical AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during development and infected with influenza virus as adults. Lungs of exposed offspring had greater bronchopulmonary inflammation compared to controls, and activated, virus-specific CD4[SUP]+[/SUP] T-cells contributed to the infiltrating leukocytes. These effects were CD4[SUP]+[/SUP] T-cell-subset specific, with increases in Th1 and regulatory T cells, but no change in the frequency of Th17 cells in the infected lung. This is in direct contrast with prior reports of suppressed conventional CD4[SUP]+[/SUP] 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[SUP]+[/SUP] 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[SUP]+[/SUP] T-cell subsets, which may contribute to differential responses to respiratory infection.
Copyright ? 2015, American Journal of Physiology - Lung Cellular and Molecular Physiology.
[h=4]KEYWORDS:[/h] CD4 T cell; aryl hydrocarbon receptor; developmental exposure; influenza virus; respiratory infection
PMID: 26071552 [PubMed - as supplied by publisher]