Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis

Julia K. Gittler, Avner Shemer, Mayte Suárez-Fariñas, Judilyn Fuentes-Duculan, Kara J. Gulewicz, Claire Q.F. Wang, Hiroshi Mitsui, Irma Cardinale, Cristina De Guzman Strong, James G. Krueger, Emma Guttman-Yassky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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 TH2 predominating in acute disease and a switch to TH1 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 TH22 and TH2 cytokines and smaller increases in IL-17 levels. A lesser induction of TH1- associated genes was detected in acute disease, although some were significantly upregulated in chronic disease. Further significant intensification of major TH22 and TH2 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 TH22 cytokines. Our findings support a model of progressive activation of TH2 and TH22 immune axes from the acute to chronic phases, expanding the prevailing view of pathogenesis with important therapeutic implications.

Original languageEnglish
Pages (from-to)1344-1354
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Issue number6
StatePublished - Dec 2012


FundersFunder number
Dermatology Foundation to Mount Sinai School of Medicine
National Institutes of HealthR00AR055948
National Institutes of Health
National Center for Research Resources
Dermatology Foundation
National Center for Advancing Translational SciencesUL1TR000043
National Center for Advancing Translational Sciences


    • Atopic dermatitis
    • IL-22
    • S100A7
    • S100A8
    • S100A9
    • T 17
    • T2
    • T22
    • acute
    • chronic
    • terminal differentiation


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