Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/13678
Title: | The Biology of Dendritic Cell Subsets in Allergen-Induced Asthma |
Authors: | Dua, Benny |
Advisor: | O`Byrne, Paul Gauvreau, Gail Larche, Mark |
Department: | Medical Sciences (Division of Physiology/Pharmacology) |
Keywords: | Asthma;Allergy;Antigen presenting cells;Dendritic cells;Myeloid dendritic cells;Plasmacytoid dendritic cells;Allergy and Immunology;Circulatory and Respiratory Physiology;Immunity;Immunopathology;Medical Immunology;Respiratory Tract Diseases;Allergy and Immunology |
Publication Date: | Apr-2014 |
Abstract: | <p>Asthma is an inflammatory disorder of the airways, and there has been growing insight into the cellular and molecular mechanisms underlying the inflammatory basis of this disease. Research into the inflammatory mechanisms of asthma has progressively shifted focus from downstream effectors, such as mast cells and eosinophils, up to Th2 lymphocytes and their proallergic cytokines. Even more upstream in the allergic cascade are dendritic cells (DCs), potent APCs that orchestrate immune responses. Evidence supporting a role of DCs in regulating airway allergic inflammation is derived mainly from animal studies. In animal models of asthma, myeloid DCs (mDCs) induce and maintain airway inflammation, while plasmacytoid DCs (pDCs) mediate tolerance and lung homeostasis. It remains uncertain, however, whether this concept of pro-allergic mDCs and anti-allergic pDCs translates from animal to human models. The overall objective of this thesis was to investigate the biology of DC subsets in allergen-induced asthma in asthmatic subjects. Initially, we demonstrate that both mDCs and pDCs increase in the airways of subjects with mild asthma after allergen inhalation. Next, we describe a distinct subpopulation of mDCs, called mDC2s, and demonstrate their association with allergy and asthma severity. Expanding on these findings, we show that mDC2s increase in the airways of mild asthmatics after allergen challenge. Lastly, we explore the potential of pharmacological therapies, anti-OX40L MAb and anti-TSLP MAb, to affect DCs in subjects with mild asthma, and demonstrate no effect of either drug on circulating DC subsets. The studies presented here provide evidence for multiple DC subtypes being involved in the regulation of allergen-induced inflammatory responses, and support continued investigations into the biology of different DC subsets in allergen-induced asthma.</p> |
Description: | <h4> </h4> |
URI: | http://hdl.handle.net/11375/13678 |
Identifier: | opendissertations/8513 9554 4801937 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Size | Format | |
---|---|---|---|
fulltext.pdf | 2.37 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.