Paternal Allergen Exposure, Offspring Asthma and Pulmonary Gamma / Delta T Cell Biology
Principle Investigator: Ian Lewkowich, PhD
The “Developmental Origin of Health and Disease” (DOHaD) hypothesis posits that early life exposures (nutritional, environmental, inflammatory) influence offspring susceptibility to a number of non-communicable diseases. Allergic asthma, a disease affecting more than 300 million people, continues to increase in prevalence. Consistent with the DoHAD hypothesis, exposures to both the mother, and the father, have been shown to influence the risk of asthma in children. The mechanisms through which maternal exposures to environmental factors influence asthma in children include altered expression of specific genes within either the egg or the developing fetus. In contrast, although specific paternal exposures (tobacco smoke, employment in specific occupations) alter offspring asthma risk in humans, the mechanisms are entirely unclear.
Our novel preliminary data using a well characterized mouse model of allergen-induced asthma demonstrate that paternal exposure to a common allergen, house dust mite (HDM), is associated with reduced asthma development in pups. Importantly, our innovative preliminary data are the first to demonstrate that paternal exposure to allergens protect from the development of asthma in offspring. This protection from asthma is associated with altered patterns of recruitment of specific cells of the immune system – T cells with a gamma / delta T cell receptor (gamma / delta T cells) – to the lung, and removing these cells from the lungs of pups, eliminates the protective effect of paternal HDM exposure strongly implying that something they are producing, is preventing asthma in these pups.
Thus, this innovative study is designed to identify the unique proteins that are produced by gamma / delta T cells, and decipher how they are limiting the development of allergic asthma. A deeper understanding of the mechanisms through which paternal exposures can influence offspring immunity will advance public health and open up new lines of research, including therapeutic avenues, for asthma and other immune disorders (e.g., autoimmune, allergic) and responses (infectious disease).