title: Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis.
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(H)2 predominating in acute disease and a switch to T(H)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.
  
  
  OBJECTIVE
  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(H)22 and T(H)2 cytokines and smaller increases in IL-17 levels. A lesser induction of T(H)1-associated genes was detected in acute disease, although some were significantly upregulated in chronic disease. Further significant intensification of major T(H)22 and T(H)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(H)2 and T(H)22 cytokines. Our findings support a model of progressive activation of T(H)2 and T(H)22 immune axes from the acute to chronic phases, expanding the prevailing view of pathogenesis with important therapeutic implications.
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Gittler
authors.forename: Avner
authors.initials: A
authors.lastname: Shemer
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Gulewicz
authors.forename: Claire Q F
authors.initials: CQ
authors.lastname: Wang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.forename: Cristina
authors.initials: C
authors.lastname: de Guzman Strong
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D003876:Dermatitis, Atopic / Q000276:immunology*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology*; D058408:Th1-Th2 Balance; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D020381:Interleukin-17; D007378:Interleukins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D000097043:Interleukin-22; C089242:S100A7 protein, human