Progressive activation of T_H2/T_H22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis

Background: Atopic dermatitis (AD) is a common disease with an increasing prevalence. The primary pathogenesis of the disease is still elusive, resulting in the lack of specific treatments. AD is currently considered a biphasic disease, with T_H2 predominating in acute disease and a switch to T_H1 characterizing chronic disease. Elucidation of the molecular factors that participate in the onset of new lesions and maintenance of chronic disease is critical for the development of targeted therapeutics. Objectives: We sought to characterize the mechanisms underlying the onset and maintenance of AD. Methods: We investigated intrapersonal sets of transcriptomes from nonlesional skin and acute and chronic lesions of 10 patients with AD through genomic, molecular, and cellular profiling. Results: Our study associated the onset of acute lesions with a striking increase in a subset of terminal differentiation proteins, specifically the cytokine-modulated S100A7, S100A8, and S100A9. Acute disease was also associated with significant increases in gene expression levels of major T_H22 and T_H2 cytokines and smaller increases in IL-17 levels. A lesser induction of T_H1- associated genes was detected in acute disease, although some were significantly upregulated in chronic disease. Further significant intensification of major T_H22 and T_H2 cytokines was observed between acute and chronic lesions. Conclusions: Our data identified increased S100A7, S100A8, and S100A9 gene expression with AD initiation and concomitant activation of T _H2 and T_H22 cytokines. Our findings support a model of progressive activation of T_H2 and T_H22 immune axes from the acute to chronic phases, expanding the prevailing view of pathogenesis with important therapeutic implications.