Cord blood dendritic cell populations in atopic-at-risk and not-at-risk infants

Abstract

Allergic disease encompasses multiple complex syndromes including hayfever, food allergies, eczema and asthma. Atopy is the genetic predisposition towards an IgE-driven immune response in reaction to environmental stimuli, and often serves as a predictor for the development of allergies in the future. While disease etiology is not yet fully understood, many factors including genetics and the environment play a role in the development of allergic disease. Reliable methods for predicting atopic disease development are crucial in emerging therapeutic approaches, which aim to decrease allergic disease severity and clinical progression through early detection and preventative measures. While DCs are emerging as key players in the development of allergic disease, they are challenging to study in vivo due to their low numbers, and ex vivo methods remain relatively unstudied. In this project, receptor expression profiles of atopic-at-risk infants compared to not-atrisk infants were examined in DCs found in cord-blood at birth and CD34+-derived DCs cultured ex vivo. Atopic-at-risks exhibited a higher percentage of ex vivo pDCs expressing TSLPR when compared to not-at-risks. Additionally, an increase of FcεRI expression in atopic-at-risks was found approaching significance in in vivo mDCs. Furthermore, DC differentiation in culture from hematopoietic progenitors and the differences between in vivo and ex vivo DCs were studied. Results indicated a consistent 10-fold increase in the DC population after a 12-day culture compared to cord blood DC numbers. Additionally, a distinct DC population emerged as early as Day 3 with a substantial increase in the percentage of mDCs relative to pDCs. A trend of increased TSLP, CD80, CD86 receptor expression and decreased TLR-5, ST2, FcεRI receptor expression after culture in both mDCs and pDCs was also noted.