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. / Thesis / Master of Science (MSc) / Allergic disease development typically begins in infancy, progressing classically in a
series of stages from early life through adulthood. Currently, there is a lack of reliable
predictive tests for the development of atopic sensitization and disease. This has slowed
efforts to intercept and prevent allergy development at its earliest stages. Dendritic cells
(DCs) link innate and adaptive immunity and are thought to be key players in the
development of allergic disease. However, the low numbers of DCs in blood make them
challenging to study. Methods such as inducing the differentiation of DCs from
progenitors are often utilized to obtain a sufficient number of cells. This project
investigates whether receptor expression of cord blood-derived DCs grown ex vivo are
comparable to the profiles of in vivo DCs at birth. Furthermore, the expression of key
receptors on DCs grown in vivo/ex vivo are compared in atopic at-risk, not-at-risk infants.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/24134 |
| Date | January 2018 |
| Creators | Strigul, Olena |
| Contributors | Denburg, Judah, Medical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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