How does exposure to diesel exhaust (DE) and inhaled allergens provoke molecular changes in the lung tissue of allergy-prone individuals?
The UBC-based lab of AllerGen investigator Dr. Christopher Carlsten is helping to answer this question. Two recent studies bring us another step closer to understanding the role of air pollution in the development and progression of allergic respiratory disease, including asthma—facilitating the design of more effective, targeted prevention strategies or interventions.
“Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers,” the result of a collaboration with the lab of AllerGen investigator Dr. Scott Tebbutt, was published in The Journal of Allergy and Clinical Immunology (JACI) in April 2016, with AllerGen trainee Dr. Chris Rider as lead author. It reports on an investigation into the effects of exposure to allergen, to DE, and to both (co-exposure) on microRNA (miRNA), gene expression and inflammatory pathways in the lung.
Fifteen study participants were subjected to a series of exposures, administered on two occasions separated by a four-week interval, including both inhalation of polluted or control air, and direct installation of allergen into different segments of the lung. Two days after each set of exposures, the researchers extracted samples of the subjects’ bronchial epithelial cells to measure changes in their gene and miRNA profiles.
They found that allergen exposure evoked a wide range of significant changes in gene and miRNA profiles measurable at 48 hours, while, in contrast, the effects of DE were more limited. They also found allergen and DE co-exposure appeared to induce unique effects, but these were not seen when the data was subjected to a conservative statistical model.
The researchers concluded that the allergen-induced changes documented by the study are “remarkable and unique,” given that most past studies measured effects only at 24 hours or earlier, that such stringent statistics were applied, and that previous co-exposure studies were focused on the upper (not lower) airway.
For a second JACI study, “Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation” (May 2016), the Carlsten lab collaborated with the lab of AllerGen investigator Dr. Michael Kobor to investigate how genes are affected by examining the role of DNA methylation in the lung’s immune response to allergens and DE.
Following the same protocol as the first study, the researchers found that exposure to either allergen or DE alone, and co-exposure to both, resulted in only minor DNA methylation within a 48-hour period. However, sequential exposures to first one (allergen or DE) and then the other four weeks later, produced a much greater effect. The study also found that effects varied according to the order of the exposures (allergen first or DE first), reflecting the high sensitivity of DNA methylation to differences in short-term exposure. The researchers concluded that “specific exposures appear to prime the lung for changes in DNA methylation induced by a subsequent insult.”
Hailed by Dr. Carlsten as “big AllerGen successes,” these studies provide further evidence that air pollution and inhaled allergens have significant allergy-relevant effects on cell biology. These insights, in turn, may contribute to improved prevention strategies and treatments for allergic diseases, especially given that current therapies do not control well for exacerbating factors such as air pollution.