title: Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis.
abstract: BACKGROUND
  Psoriasis and atopic dermatitis (AD) are common, complex inflammatory skin diseases. Both diseases display immune infiltrates in lesions and epidermal growth/differentiation alterations associated with a defective skin barrier. An incomplete understanding of differences between these diseases makes it difficult to compare human disease pathology to animal disease models.
  
  
  OBJECTIVE
  To characterize differences between these diseases in expression of genes related to epidermal growth/differentiation and inflammatory circuits.
  
  
  METHODS
  We performed genomic profiling of mRNA in chronic psoriasis (n = 15) and AD (n = 18) skin lesions compared with normal human skin (n = 15).
  
  
  RESULTS
  As expected, clear disease classifications could be constructed on the basis of expected immune polarity (T(H)1, T(H)2, T(H)17) differences. However, even more striking differences were identified in epidermal differentiation programs that could be used for precise disease classifications. Although both psoriasis and AD skin lesions displayed regenerative epidermal hyperplasia, which is a general alteration in epidermal growth, keratinocyte terminal differentiation was differentially polarized. In AD, we found selective defects in expression of multiple genes encoding the cornified envelope, with the largest alteration in loricrin (expressed at 2% of the level of normal skin). At the ultrastructural level, the cornified envelope in AD was broadly defective with highly decreased compaction of corneocytes and reduced intercellular lipids. Hence, the entire keratinocyte terminal differentiation program (cytoplasmic compaction, cornification, and lipid release) is defective in AD, potentially underlying the immune differences.
  
  
  CONCLUSIONS
  Our study shows that although alterations in barrier responses exist in both diseases, epidermal differentiation is differentially polarized, with major implications for primary disease pathogenesis.
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY 10065, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Andrea
authors.initials: A
authors.lastname: Chiricozzi
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Nograles
authors.forename: Avner
authors.initials: A
authors.lastname: Shemer
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.forename: Peng
authors.initials: P
authors.lastname: Lin
authors.forename: Reuven
authors.initials: R
authors.lastname: Bergman
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation; D004817:Epidermis / Q000648:ultrastructure*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult