Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation

Abstract

Background 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. Objective 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. Methods 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. Results 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. Conclusion These data are evidence that neutrophilic inflammation is a feature of lesional atopic dermatitis pathology, comorbid with allergic inflammation.

Immunomodulation in Patients with Chronic Hand Eczema Treated with Oral Alitretinoin

“…Th17 cells are proinflammatory via stimulation of keratinocytes to produce cytokines, chemokines, and vascular endothelial growth factor. Moreover, we have previously shown that increased numbers of Th17 cells are detectable in AD patients and that IL-17 promotes IgE production in vitro [23,24]. …”

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2012

“…112 Recently, a comparative transcriptomic analysis of AD and psoriasis revealed evidence for increased IL17 gene expression and shared neutrophilic inflammation in patients with these 2 skin diseases. 113 However, future studies are needed to determine whether IL-17 expression in the T H 2/T H 22 cytokine environment of AD would lead to different biologic responses than seen in the polarized T H 1/IL-17 environment of psoriasis.…”

Deciphering the complexities of atopic dermatitis: Shifting paradigms in treatment approaches

“…The best biomarkers for AD currently define patients who are Th2 polarized vs those who are not. In the future a combination of epidermal proteomics, genomics, gene transcriptomes, blood biomarkers in combination with the clinical phenotype will offer more precision in defining endotypes of AD (118)(119)(120). Approximately 80% of AD patients have elevated serum IgE levels, often with increased eosinophilia and serum levels of the Th2 chemokine thymus and activation regulated chemokine (TARC).…”