1. Psoriasis-Associated Late Cornified Envelope (LCE) Proteins Have Antibacterial Activity
- Author
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Niehues, H., Tsoi, L.C., Krieken, D.A. van der, Jansen, P.A.M., Oortveld, M.A.W., Rodijk-Olthuis, D., Vlijmen, I.M.J.J. van, Hendriks, W.J.A.J., Helder, R.W.J., Bouwstra, J.A., Bogaard, E.H. van den, Stuart, P.E., Nair, R.P., Elder, J.T., Zeeuwen, P.L.J.M., Schalkwijk, J., Krieken, D. A. van der, Oortveld, M.A.W, Krieken, D. A. van der, and Oortveld, M.A.W
- Subjects
Keratinocytes ,Male ,0301 basic medicine ,Genotype ,Human skin ,Dermatology ,Quantitative trait locus ,Biology ,Real-Time Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Biochemistry ,Linkage Disequilibrium ,Article ,Cornified envelope ,03 medical and health sciences ,Cornified Envelope Proline-Rich Proteins ,Psoriasis ,medicine ,Stratum corneum ,Humans ,Life Science ,Genetic Predisposition to Disease ,Molecular Biology ,Gene ,Cells, Cultured ,integumentary system ,Biopsy, Needle ,Other Research Radboud Institute for Health Sciences [Radboudumc 0] ,Role ,Wild type ,Cell Biology ,medicine.disease ,Immunohistochemistry ,Immunity, Innate ,Anti-Bacterial Agents ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Immunology ,Female ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] ,Function (biology) ,Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] - Abstract
Contains fulltext : 182646.pdf (Publisher’s version ) (Open Access) Terminally differentiating epidermal keratinocytes express a large number of structural and antimicrobial proteins that are involved in the physical barrier function of the stratum corneum and provide innate cutaneous host defense. Late cornified envelope (LCE) genes, located in the epidermal differentiation complex on chromosome 1, encode a family of 18 proteins of unknown function, whose expression is largely restricted to epidermis. Deletion of two members, LCE3B and LCE3C (LCE3B/C-del), is a widely-replicated psoriasis risk factor that interacts with the major psoriasis-psoriasis risk gene HLA-C*06. Here we performed quantitative trait locus analysis, utilizing RNA-seq data from human skin and found that LCE3B/C-del was associated with a markedly increased expression of LCE3A, a gene directly adjacent to LCE3B/C-del. We confirmed these findings in a 3-dimensional skin model using primary keratinocytes from LCE3B/C-del genotyped donors. Functional analysis revealed that LCE3 proteins, and LCE3A in particular, have defensin-like antimicrobial activity against a variety of bacterial taxa at low micromolar concentrations. No genotype-dependent effect was observed for the inside-out or outside-in physical skin barrier function. Our findings identify an unknown biological function for LCE3 proteins and suggest a role in epidermal host defense and LCE3B/C-del-mediated psoriasis risk.
- Published
- 2017
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