Atopic dermatitis (AD) is a common skin disease that is characterized by chronic, relapsing skin inflammation and eczematous, itchy lesions. In AD, systemic and local eosinophilia and basophilia is thought to contribute to disease progression in both acute and chronic lesions. It has been previously shown that in chronic allergic inflammatory diseases, tissue eosinophilia and basophilia may in part result from eosinophil/basophil (Eo/B) progenitors trafficking from the bone marrow and maturing in tissue in response to type 2 cytokines including IL-5 and IL-3. We therefore proposed that a similar mechanism could be contributing to the pathogenesis of AD. First, we compared lesional and non-lesional AD tissue, and found approximately 10-fold higher levels of Eo/B progenitors in the lesional tissue (p<0.05). As previous research has shown an increase in Eo/B progenitors in the airways of allergic asthmatics post inhaled allergen challenge, we next examined whether Eo/B progenitors increased locally in the acute phase of AD using the intradermal allergen challenge model. Compared to intradermal diluent challenge there was an increase in Eo/B progenitors (5.5-fold), eosinophils (18-fold) and basophils (2.5-fold) 24 hours post intradermal allergen challenge (all p<0.05). These increases were consistent with findings in allergic airways. Lastly, we examined the relationship between disease severity and Eo/B progenitors in inflamed lesional (chronic) and allergen-challenged (acute) tissue. We found that Eo/B progenitors in lesional tissue positively correlated with disease severity (EASI R=0.71, p<0.05 and SCORAD R=0.65, p<0.05), while in allergen-challenged tissue a trend was seen for a positive correlation between Eo/B progenitors and disease severity (EASI R=0.48, p=0.07 and SCORAD R=0.46, p=0.09). These results highlight the potential involvement of Eo/B progenitors in the disease pathogenesis of AD. / Thesis / Master of Science (MSc) / Atopic dermatitis is a common skin disease that is characterized by chronic, relapsing skin inflammation and eczematous, itchy lesions. In other allergic diseases, a cell called the “eosinophil/basophil progenitor” contributes to the accumulation of inflammatory cells in the diseased organ. We proposed that eosinophil/basophil progenitors found in the skin may be contributing to the development of local allergic inflammation. In patients with moderate-to-severe atopic dermatitis we compared acute responses to intradermal allergen and chronic skin lesions to diluent-challenged and un-affected skin, respectively. Allergen-challenged skin had more eosinophil/basophil progenitors, mature eosinophils and basophils 24 hours’ post-challenge compared to unchallenged skin (p<0.05). Chronic skin lesions had more eosinophil/basophil progenitors than un-affected skin (p<0.05). The number of eosinophil/basophil progenitors positively correlated to disease severity as determined by EASI and SCORAD. Our results suggest that accumulation of eosinophil/basophil progenitors in skin of atopic dermatitis patients could support allergic inflammation and contribute to disease severity.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23420 |
| Date | January 2018 |
| Creators | Price, Emma L |
| Contributors | Gauvreau, Gail M, Medical Sciences (Division of Physiology/Pharmacology) |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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