Atopic dermatitis and psoriasis are common inflammatory diseases, canonically described as involving distinct T-helper polarization and granulocytic infiltration. Acute atopic dermatitis lesions are associated with TH2 and eosinophilic inflammation, while psoriasis lesions are associated with TH1/17 and neutrophilic inflammation. Despite intensive investigation, these pathways remain incompletely understood in vivo in human subjects.
Using atopic dermatitis and psoriasis lesional skin as exemplar TH2 and TH1/17 diseased tissue, we sought to clarify common and unique molecular and pathophysiologic features in inflamed skin with different types of inflammatory polarization.
We conducted gene expression microarray analyses to identify distinct and commonly dysregulated expression in atopic dermatitis (by Hanifin & Rajka criteria) and psoriasis lesions. We defined gene sets comprising genes encoding cytokines, chemokines, and growth factors that were uniquely or jointly dysregulated in atopic dermatitis and psoriasis, and calculated aggregate gene set expression scores for lesional skin of these dermatoses and healthy control skin.
The atopic dermatitis gene set score correlated with systemic and local measures of allergic inflammation including serum IgE, blood eosinophil count, and tissue eosinophils. Unexpectedly, genes encoding neutrophil chemoattractants among the common gene set were highly expressed in atopic dermatitis lesional skin. H&E and immunohistochemical analyses showed the numbers of neutrophils in atopic dermatitis lesional skin were comparable to those in psoriasis lesional skin, and both were correlated with the extent of expression of neutrophil chemoattractant genes.
These data are evidence that neutrophilic inflammation is a feature of lesional atopic dermatitis pathology, comorbid with allergic inflammation.