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

Authors :
Gittler, Julia K.
Shemer, Avner
Suárez-Fariñas, Mayte
Fuentes-Duculan, Judilyn
Gulewicz, Kara J.
Wang, Claire Q.F.
Mitsui, Hiroshi
Cardinale, Irma
de Guzman Strong, Cristina
Krueger, James G.
Guttman-Yassky, Emma
Source :
Journal of Allergy & Clinical Immunology; Dec2012, Vol. 130 Issue 6, p1344-1354, 11p
Publication Year :
2012

Abstract

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<subscript>H</subscript>2 predominating in acute disease and a switch to T<subscript>H</subscript>1 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<subscript>H</subscript>22 and T<subscript>H</subscript>2 cytokines and smaller increases in IL-17 levels. A lesser induction of T<subscript>H</subscript>1-associated genes was detected in acute disease, although some were significantly upregulated in chronic disease. Further significant intensification of major T<subscript>H</subscript>22 and T<subscript>H</subscript>2 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<subscript>H</subscript>2 and T<subscript>H</subscript>22 cytokines. Our findings support a model of progressive activation of T<subscript>H</subscript>2 and T<subscript>H</subscript>22 immune axes from the acute to chronic phases, expanding the prevailing view of pathogenesis with important therapeutic implications. [Copyright &y& Elsevier]

Details

Language :
English
ISSN :
00916749
Volume :
130
Issue :
6
Database :
Supplemental Index
Journal :
Journal of Allergy & Clinical Immunology
Publication Type :
Academic Journal
Accession number :
83875617
Full Text :
https://doi.org/10.1016/j.jaci.2012.07.012