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
Related in: MedlinePlus
Mentions: Neutralization of TSLP completely abrogated the atopic dermatitis phenotype in TPA treated EPI−/− mice (Figure 7A). Anti-NKG2D also reduced the atopic phenotype, albeit to a lesser extent (Figures 7A and 8). TPA-induced epidermal thickening was significantly reduced in TSLP or NKG2D suppressive conditions, without any differential effect on the number of PH3+ basal layer cells (Figure 7A,C, D). TSLP treatment reduced the transit time of BrdU + cells from the basal to the outermost granular layers since although the epidermis was thinner the proportion of labelled granular cells was unaffected (Figure 7E,F). There was a slight reduction in hyperkeratosis, and parakeratosis was clearly decreased (Figure 7G,H). Targeting the Rae-1/NKG2D/TSLP axis also reduced the number of dermal CD4+CD3+ lymphocytes, mast cells, eosinophils, and epidermal pustules in EPI−/− mice (Figure 8A–D). Furthermore, under TSLP suppressive conditions the number of epidermal DETCs was increased in EPI−/− skin (Figure 8E). Macrophage numbers were unaffected by TSLP or NKG2D blockade (data not shown).10.7554/eLife.01888.010Figure 8.Effects of TSLP and NKG2D inhibition and quantitation of cytokine levels in SCCs.
Affiliation: Centre for Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom.