EOSINOPHIL/BASOPHIL PROGENITORS: A POSSIBLE ROLE IN THE PATHOGENESIS OF ATOPIC DERMATITIS

Abstract

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.