Epidermal barrier defects link atopic dermatitis with altered skin cancer susceptibility.
Bottom Line: Atopic dermatitis can result from loss of structural proteins in the outermost epidermal layers, leading to a defective epidermal barrier.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.
Affiliation: Centre for Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom.Show MeSH
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Mentions: EPI−/− mice exhibited an exacerbated response to TPA (Figure 3A). Their skin was reddened, dry and scaly, whereas that of WT mice was not (data not shown). Histological analysis revealed increased hyperkeratosis (thickened stratum corneum) and parakeratosis (retention of nuclei in cornified cells) (Figure 3B,C), consistent with defective desquamation (Sevilla et al., 2007). Widening of intercellular spaces in the epidermal basal layer (spongiosis) was extensive in EPI−/− but not WT skin (Figure 3A). Epidermal thickness, measured as the distance from the basal to the upper granular layer, was greater in EPI−/− mice treated with TPA or DMBA/TPA than in WT mice, and this correlated with a greater number of suprabasal layers (Figure 3A,D). The numbers of keratinocytes with dsDNA breaks and active caspase-3 were similar in EPI−/− and WT epidermis (Figure 3F,G).10.7554/eLife.01888.005Figure 3.Keratinocyte responses to TPA treatment.
Affiliation: Centre for Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom.