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Psoriasis-Associated Late Cornified Envelope (LCE) Proteins Have Antibacterial Activity
- Source :
- Journal of Investigative Dermatology, 137(11), 2380-2388, Journal of Investigative Dermatology 137 (2017) 11, Journal of Investigative Dermatology, 137, 11, pp. 2380-2388, Journal of Investigative Dermatology, 137, 2380-2388, JOURNAL OF INVESTIGATIVE DERMATOLOGY, 137(11), 2380-2388, JOURNAL OF INVESTIGATIVE DERMATOLOGY, J Invest Dermatol
- Publication Year :
- 2017
-
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.
- 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]
Subjects
Details
- Language :
- English
- ISSN :
- 0022202X
- Volume :
- 137
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....95a7b7c34df04512ae5e7cee170f1699