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 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 language | English (US) |
|---|---|
| Pages (from-to) | 1344-1354 |
| Number of pages | 11 |
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 130 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 1 2012 |
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Keywords
- acute
- Atopic dermatitis
- chronic
- IL-22
- S100A7
- S100A8
- S100A9
- T 17
- T2
- T22
- terminal differentiation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. / 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.
In: Journal of Allergy and Clinical Immunology, Vol. 130, No. 6, 01.12.2012, p. 1344-1354.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis
AU - Gittler, Julia K.
AU - Shemer, Avner
AU - Suárez-Fariñas, Mayte
AU - Fuentes-Duculan, Judilyn
AU - Gulewicz, Kara J.
AU - Wang, Claire Q.F.
AU - Mitsui, Hiroshi
AU - Cardinale, Irma
AU - De Guzman Strong, Cristina
AU - Krueger, James G.
AU - Guttman-Yassky, Emma
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
AB - 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.
KW - acute
KW - Atopic dermatitis
KW - chronic
KW - IL-22
KW - S100A7
KW - S100A8
KW - S100A9
KW - T 17
KW - T2
KW - T22
KW - terminal differentiation
UR - http://www.scopus.com/inward/record.url?scp=84870294267&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870294267&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2012.07.012
DO - 10.1016/j.jaci.2012.07.012
M3 - Article
C2 - 22951056
AN - SCOPUS:84870294267
VL - 130
SP - 1344
EP - 1354
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 6
ER -