Epidermal barrier defects link atopic dermatitis with altered skin cancer susceptibility.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 24843010.
- Also identified by DOI 10.7554/eLife.01888 and PMC identifier 4007207.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Atopic dermatitis can result from loss of structural proteins in the outermost epidermal layers, leading to a defective epidermal barrier. To test whether this influences tumour formation, we chemically induced tumours in EPI-/- mice, which lack three barrier proteins-Envoplakin, Periplakin, and Involucrin. EPI-/- mice were highly resistant to developing benign tumours when treated with 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). The DMBA response was normal, but EPI-/- skin exhibited an exaggerated atopic response to TPA, characterised by abnormal epidermal differentiation, a complex immune infiltrate and elevated serum thymic stromal lymphopoietin (TSLP). The exacerbated TPA response could be normalised by blocking TSLP or the immunoreceptor NKG2D but not CD4+ T cells. We conclude that atopy is protective against skin cancer in our experimental model and that the mechanism involves keratinocytes communicating with cells of the immune system via signalling elements that normally protect against environmental assaults.DOI: http://dx.doi.org/10.7554/eLife.01888.001.
Medical subject headings
- Carcinoma, Squamous Cell
- Cell Transformation, Neoplastic
- Dermatitis, Atopic
- Epidermis
- Membrane Proteins
- Papilloma
- Plakins
- Protein Precursors
- Skin Neoplasms