AhR Regulation of the Mature Immune System
Infectious diseases remain a major cause of illness and death. Conventional thinking is that fighting infection is a race between a pathogen's ability to evade host defenses and multiply, and the host's ability to destroy it. Research by our group challenges this paradigm with a novel concept: environmental factors play a fundamental role in the ultimate outcome of an infection. For example, emerging epidemiological evidence supports the idea that exposures to common environmental chemicals deregulate immune responses to respiratory infections. Other studies show that exposure to pollutants correlates with poorer antibody responses to routine immunizations. The public health implications of these observations are profound, especially for at-risk populations. However, the mechanisms by which environmental agents modulate host responses to infections remain largely unexplored.
Within our laboratory, we seek to understand how an environment-sensing, ligand-activated transcription factor, called the aryl hydrocarbon receptor (AHR), modulates the magnitude and nature of the host's protective response to infection. For the most part, we accomplish this research using human influenza viruses, and use them to interrogate how the AHR modifies the response of different types of immune cells to influence the outcome from infection. We use a variety of genetic tools, including the LoxP-Cre system to conditionally ablate AhR in specific cell lineages, contemporary flow cytometry, including ImageStream technology, and numerous immunological, pharmacological and biochemical approaches to understand the cell-type specific manner in which AHR regulates the immune system.
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