Connecting environmental exposures with allergic and respiratory outcomes - The ongoing study of the Kingston Allergy Birth Cohort
Atopic diseases like allergies and asthma are mediated by several types of immune cells such as Regulatory T cells (Treg), and T helper type 1, 2, and 17 (Th1, Th2, and Th17) cells. Reductions in Treg numbers and the Th1:Th2 ratio and increases in Th17 cells have been related to atopic disease pathogenesis; however, whether these are a cause or result of disease remains unclear. Moreover, researchers have identified several early life environmental exposures that contribute to allergic disease development. However, these is a lack in understanding of how these exposures relate to changes at the cellular and genetic level, and how these exposures contribute to atopic disease progression. We polarized T helper cells from umbilical cord blood mononuclear cell (CBMC) samples from children with high (n=3) and low (n=4) atopic risk. We gathered information on the home environment of 92 mother child pairs, determined the odds ratio (OR) of a positive SPT (SPT) at 2 years with exposure to indoor air pollutants, and compared the number of different exposures between SPT positive and negative at 2 years. Lastly, we attained prenatal and current exposure data to air pollutants of 39 mother child pairs at 6 to 7 years of age and collected a blood samples from the 24 children. We determined the relationships between exposure to air pollutants with sensitization, cough/wheeze, plasma cytokine levels, Treg and Th17 frequencies, and FOXP3 expression. High atopic risk CBMC samples had higher Th17 frequencies following T cell polarization. The OR of a positive SPT at 2 years was increased with exposure to candles, cats, and environmental tobacco smoke. 2 year old children with a positive SPT had more exposures at each time point than children with a negative SPT. Children with atopic disease at 6 to7 years had reductions in the regulatory/inflammatory cytokine ratios and children with exposures to cats and high levels of indoor air pollutants had lower plasma cytokine levels. FOXP3 expression was elevated in atopic children and in children with exposure to air pollution. This work provides evidence supporting the importance of the early life environment to atopic disease development.