title: Late cornified envelope (LCE) proteins: distinct expression patterns of LCE2 and LCE3 members suggest nonredundant roles in human epidermis and other epithelia.
abstract: BACKGROUND
  Deletion of the late cornified envelope (LCE) proteins LCE3B and LCE3C is a strong and widely replicated psoriasis risk factor. It is amenable to biological analysis because it precludes the expression of two epidermis-specific proteins, rather than being a single-nucleotide polymorphism of uncertain significance. The biology of the 18-member LCE family of highly homologous proteins has remained largely unexplored so far.
  
  
  OBJECTIVE
  To analyse LCE3 expression at the protein level in human epithelia, as a starting point for functional analyses of these proteins in health and disease.
  
  
  METHODS
  We generated the first pan-LCE3 monoclonal antibody and provide a detailed analysis of its specificity towards individual LCE members. LCE2 and LCE3 expression in human tissues and in reconstructed human skin models was studied using immunohistochemical analyses and quantitative polymerase chain reaction.
  
  
  RESULTS
  Our study reveals that LCE2 and LCE3 proteins are differentially expressed in human epidermis, and colocalize only in the upper stratum granulosum layer. Using an in vitro reconstructed human skin model that mimics epidermal morphogenesis, we found that LCE3 proteins are expressed at an early time point during epidermal differentiation in the suprabasal layers, while LCE2 proteins are found only in the uppermost granular layer and stratum corneum.
  
  
  CONCLUSIONS
  Based on the localization of LCE2 and LCE3 in human epidermis we conclude that members of the LCE protein family are likely to have distinct functions in epidermal biology. This finding may contribute to understanding why LCE3B/C deletion increases psoriasis risk.
authors.affiliation: Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Niehues
authors.affiliation: Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.
authors.forename: I M J J
authors.initials: IM
authors.lastname: van Vlijmen-Willems
authors.affiliation: Massachusetts General Hospital/Harvard Medical School, Boston, MA, U.S.A.
authors.forename: J G M
authors.initials: JG
authors.lastname: Bergboer
authors.affiliation: Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.
authors.forename: F F J
authors.initials: FF
authors.lastname: Kersten
authors.affiliation: Cancer Research U.K. Cambridge Institute, University of Cambridge, The Li Ka Shing Centre, Cambridge, U.K.
authors.forename: M
authors.initials: M
authors.lastname: Narita
authors.affiliation: Department of Cell Biology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.
authors.forename: W J A J
authors.initials: WJ
authors.lastname: Hendriks
authors.affiliation: Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: van den Bogaard
authors.affiliation: Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.
authors.forename: P L J M
authors.initials: PL
authors.lastname: Zeeuwen
authors.affiliation: Department of Dermatology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Schalkwijk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D055233:Cornified Envelope Proline-Rich Proteins / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008875:Middle Aged; D008954:Models, Biological; D009061:Mouth Mucosa / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism; D055815:Young Adult
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins