Leffler J, Mincham KT, Holt PG, Strickland DH
Increasing prevalence of immunological sensitization has been identified as a key risk factor for allergic asthma. The nature of the immunological mechanisms that underlie generation of mucosal IgE sensitization, as opposed to the normal response of protective tolerance to aeroallergens, remains unclear. To identify mechanisms promoting sensitization versus tolerance we use a two-strain experimental rat model where one strain is susceptible to sensitization after repeated allergen exposure whereas the other is non-susceptible and develops tolerance. We have observed that the non-susceptible strain has a larger proportion of regulatory T cells in their airways and that this prevents activation and tissue destruction by Th2 effector cells. We have previously demonstrated that the ability of airway mucosal dendritic cells to sample and transport allergens from the airways to the draining lymph nodes where T cells are induced is crucial to ensure a regulatory response. In line with this, we have shown that exposure to a high dose of allergen can be protective and prevent airway hyper responsiveness. We hypothese that effective allergen uptake is essential to induce tolerance upon primary exposure and have observed that this ability differ between the two strains during repeated exposures. We have also observed differences in the dendritic cell subset composition in the airways and this is something we are currently analysing.
Plain language summary: Some people are more likely than others to develop allergies to substances contained within the air we breathe. Children of parents with allergies have a higher risk of having allergies and of developing allergic asthma. How and why allergies develop is still not fully understood. This project investigates how cells of the immune system respond to substances to cause allergies. This information will potentially help us to develop new treatments aimed at preventing the development of allergic disease.
Funder: National Health and Medical Research Council of Australia.